Tachycardia - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

TACHYCARDIA A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Tachycardia: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-84646-4 1. Tachycardia-Popular works. I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International, Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on tachycardia. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.

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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.

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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes&Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON TACHYCARDIA .......................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Tachycardia ................................................................................... 7 E-Journals: PubMed Central ....................................................................................................... 65 The National Library of Medicine: PubMed ................................................................................ 68 CHAPTER 2. NUTRITION AND TACHYCARDIA .............................................................................. 115 Overview.................................................................................................................................... 115 Finding Nutrition Studies on Tachycardia................................................................................ 115 Federal Resources on Nutrition ................................................................................................. 118 Additional Web Resources ......................................................................................................... 119 CHAPTER 3. ALTERNATIVE MEDICINE AND TACHYCARDIA ........................................................ 121 Overview.................................................................................................................................... 121 National Center for Complementary and Alternative Medicine................................................ 121 Additional Web Resources ......................................................................................................... 129 General References ..................................................................................................................... 131 CHAPTER 4. DISSERTATIONS ON TACHYCARDIA .......................................................................... 133 Overview.................................................................................................................................... 133 Dissertations on Tachycardia..................................................................................................... 133 Keeping Current ........................................................................................................................ 133 CHAPTER 5. PATENTS ON TACHYCARDIA .................................................................................... 135 Overview.................................................................................................................................... 135 Patents on Tachycardia.............................................................................................................. 135 Patent Applications on Tachycardia .......................................................................................... 158 Keeping Current ........................................................................................................................ 190 CHAPTER 6. BOOKS ON TACHYCARDIA ........................................................................................ 191 Overview.................................................................................................................................... 191 Book Summaries: Online Booksellers......................................................................................... 191 Chapters on Tachycardia............................................................................................................ 192 CHAPTER 7. PERIODICALS AND NEWS ON TACHYCARDIA .......................................................... 193 Overview.................................................................................................................................... 193 News Services and Press Releases.............................................................................................. 193 Academic Periodicals covering Tachycardia .............................................................................. 195 CHAPTER 8. RESEARCHING MEDICATIONS .................................................................................. 197 Overview.................................................................................................................................... 197 U.S. Pharmacopeia..................................................................................................................... 197 Commercial Databases ............................................................................................................... 198 Researching Orphan Drugs ....................................................................................................... 198 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 203 Overview.................................................................................................................................... 203 NIH Guidelines.......................................................................................................................... 203 NIH Databases........................................................................................................................... 205 Other Commercial Databases..................................................................................................... 207 The Genome Project and Tachycardia........................................................................................ 207 APPENDIX B. PATIENT RESOURCES ............................................................................................... 213 Overview.................................................................................................................................... 213 Patient Guideline Sources.......................................................................................................... 213 Finding Associations.................................................................................................................. 236 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 239 Overview.................................................................................................................................... 239

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Preparation................................................................................................................................. 239 Finding a Local Medical Library................................................................................................ 239 Medical Libraries in the U.S. and Canada ................................................................................. 239 ONLINE GLOSSARIES................................................................................................................ 245 Online Dictionary Directories ................................................................................................... 245 TACHYCARDIA DICTIONARY ................................................................................................ 247 INDEX .............................................................................................................................................. 327

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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with tachycardia is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about tachycardia, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to tachycardia, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on tachycardia. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to tachycardia, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on tachycardia. The Editors

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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

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CHAPTER 1. STUDIES ON TACHYCARDIA Overview In this chapter, we will show you how to locate peer-reviewed references and studies on tachycardia.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and tachycardia, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “tachycardia” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •

Dentoalveolar Abscess in a Pediatric Patient With Ketoacidosis Caused by Occult Diabetes Mellitus Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontics. 88(2): 164-166. August 1999. Summary: Oral health professionals are frequently asked to evaluate patients with routine odontogenic infections (infections arising from the dentition and its supporting structures). These patients can sometimes present with systemic signs and symptoms, including fever, malaise, tachycardia (racing heartbeat), and dehydration. In this article, the authors present the case of a pediatric patient with a routine canine space infection who exhibited classic clinical signs and symptoms of diabetic ketoacidosis. Their report illustrates the importance of a comprehensive approach to patient evaluation and diagnosis in a case that might otherwise have been interpreted as a simple odontogenic

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infection. Clues to the patient's underlying systemic problem came from the history obtained from the parents. It is also critical in a patient with a severe odontogenic infection who appears ill and dehydrated that electrolyte levels and a complete blood count be obtained to evaluate the fluid status. Information regarding the severity of the infection should be gathered, and the possibility of a systemic disease such as diabetes should be ruled out. The author concludes that oral health professionals need to be aware of the signs and symptoms of common systemic diseases that may initially manifest themselves in connection with a dental oral complaint. 1 figure. 4 references. •

Life-Threatening Retroperitoneal Sepsis After Hemorrhoid Injection Sclerotherapy: Report of a Case Source: Diseases of the Colon and Rectum. 42(3): 421-423. March 1999. Contact: Available from Williams and Wilkins. 352 West Camden Street, Baltimore, MD 21201-2436. Summary: This article reports a case of life threatening retroperitoneal sepsis after injection sclerotherapy for first degree hemorrhoids. A 50 year old man with symptomatic first degree hemorrhoids was seen in the outpatient department. An experienced surgical registrar injected three internal hemorrhoids with 3 to 5 mL of 5 percent oily phenol. Four days later, the patient was admitted as an emergency, complaining of tight central chest pain. For 6 hours he had experienced chills and pelvic pain radiating to his lower abdomen and the backs of his thighs. Anorectal instrumentation was not attempted, because the patient was reporting severe pelvic pain. Investigation revealed leukocytosis, raised creatinine kinase, and electrocardiographic changes suggestive of anteroseptal myocardial infarction. Streptokinase, cefotaxime, and metronidazole were administered. Later that day, his pelvic pain worsened. He remained pyrexial (having a fever), developed tachycardia (rapid heartbeat), and went into urinary retention. Computed tomography revealed extensive retroperitoneal fluid but no localized abscess. Blood culture isolated gram negative bacilli, but exploratory laparotomy found no colonic lesion. The fecal stream was diverted with an end sigmoid colostomy and the rectal stump was oversewn. Hyperbaric oxygen, antibiotics, and intensive inotropic and ventilatory support were continued in the postoperative period. The patient eventually made a good recovery. The authors note that life threatening sepsis after injection sclerotherapy for hemorrhoids has been reported only once previously. One table summarizes the cases of life threatening complications after rubber band ligation of hemorrhoids. 1 table. 9 references.

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Colitis: Key Components of the Evaluation Source: Consultant. 38(2): 375-378, 381-383. February 1998. Contact: Available from Cliggott Publishing Company. 55 Holly Hill Lane, Box 4010, Greenwich, CT 06831-0010. Summary: This article reviews the key components of the evaluation of colitis. Colitis is a nonspecific condition that has a variety of causes, including inflammatory bowel disease, infections, ischemia, radiation, and antibiotic therapy. The mainstays of evaluating patients who have colitis include the history and physical examination, sigmoidoscopy with mucosal biopsy, stool examination, and barium radiography. These tools are used to determine if colitis is present, how severe it is, the cause of the colitis, and the anatomic extent of the disease. In addition to the typical symptoms of colitis (diarrhea, abdominal pain, and tenesmus), the authors recommend that physicians look

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for signs of more severe disease, such as orthostasis, pallor, fever, fatigue, and tachycardia. Also, physicians should be alert for extraintestinal manifestations of chronic inflammatory bowel disease (IBD), such as mouth ulcers, erythema nodosum, and arthritis. Laboratory findings that may suggest severe colitis include a low hemoglobin level, leukocytosis, an elevated erythrocyte sedimentation rate, and hypoalbuminemia. After confirming the presence of colitis with proctosigmoidoscopy or flexible sigmoidoscopy, stool cultures and parasite testing should be ordered to identify the specific cause. Complications of colitis include toxic megacolon, perforation, hemorrhage, and obstruction in ischemic disease. 4 figures. 3 tables. 16 references. (AAM). •

Refeeding the Malnourished Patient (editorial) Source: Current Opinion in Gastroenterology. 15(2): 151-153. March 1999. Contact: Available from Lippincott Williams and Wilkins Publishers. 12107 Insurance Way, Hagerstown, MD 21740. (800) 637-3030. Fax (301) 824-7390. Summary: This editorial review article addresses refeeding of the severely malnourished patient, a technique that is necessary to reverse the adverse effects of malnutrition and to prevent death from starvation. The goal in refeeding such patients is to inhibit the mobilization of endogenous fuels, using ingested or infused nutrients to meet the body's nutritional requirements and to rebuild lost nutrient stores. The author cautions that, because of the structural, functional, and metabolic alterations caused by previously inadequate food intake, injudicious nutritional therapy can have adverse clinical consequences. Cardiovascular complications related to impaired muscle function are characteristic of the refeeding syndrome. The most worrisome electrolyte abnormality is hypophosphatemia, which can cause acute respiratory failure, arterial hypotension, tachycardia, and death. The author offers clinical recommendations, stating that it is important to be particularly cautious in providing nutritional therapy to cachectic, chronically semistarved patients to avoid complications during refeeding. Daily monitoring of body weight, fluid intake, urine output, and plasma glucose and electrolyte values is critical during early refeeding, because the risk of complications is greatest during the first week of therapy. 33 references (5 annotated).

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Treatment of Acute Porphyria Source: Hospital Medicine. 62(7): 422-425. July 2001. Summary: This journal article provides health professionals with information on the treatment of acute porphyria. Acute attacks are often triggered by drugs, hormones, alcohol, or calorie restriction. They are more common in women and usually first occur between the ages of 15 and 40 years. As soon as an acute attack is suspected, any drugs or other potential triggers should be withdrawn and appropriate supportive treatments started using drugs that are safe in acute porphyria. Opiates are the most effective analgesics for treating an acute attack. Hyponatremia is common, so careful management of intravenous fluids, with electrolyte measurement at least twice daily and avoidance of hypotonic solutions whenever possible, is important. Cardiovascular complications such as hypertension and tachycardia are rarely sufficiently severe to require therapy. Impaired nutrition may aggravate porphyria, so adequate calorie intake is also important. Attacks of acute porphyria are associated with increased activity of hepatic 5-aminolevulinate (ALA) synthase, overproduction of ALA, and relative haem (heme) deficiency. Carbohydrate loading and parenteral administration of haem (heme) are two procedures that have been used successfully for the specific treatment of attacks

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of acute porphyria. Carbohydrate loading with 2 liters of 20 percent glucose over 24 hours in divided doses of 500 milliliters was the recommended regimen for treating an acute attack prior to the introduction of hem. The introduction of haem (heme) arginate has substantially improved the treatment of acute attacks of porphyria. Haem (heme) arginate should be administered as soon as the diagnosis is established, preferably within 48 hours of symptom onset. Haem (heme) arginate has a greater metabolic effect and leads to a better clinical outcome than carbohydrate loading. In addition, it is easier to administer, avoids the danger of water overload, and has very few adverse effects. The article concludes that haem (heme) arginate should replace glucose loading as the specific treatment for acute porphyria. 3 tables and 18 references. •

Cardiovascular Autonomic Neuropathy: Clinical Manifestations and Measurement Source: Diabetes Reviews. 7(4): 342-357. 1999. Contact: Available from American Diabetes Association, Inc. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Summary: This review article provides information on the epidemiology, pathogenesis, clinical manifestations, measurement, and outcome of cardiovascular autonomic neuropathy (CAN). Several prospective studies have demonstrated an increased mortality among diabetic patients who have CAN. The overall mortality rates over periods up to 10 years were approximately 27 percent in diabetic patients with CAN detected by reduced heart rate variability (HRV) compared with 5 percent in those without evidence of CAN. However, reduced HRV is an independent indicator of poor prognosis in the absence of diabetes, as a consequence of common cardiovascular diseases such as coronary artery disease, myocardial infarction, and heart failure. Besides reduced HRV, the clinical manifestations of CAN include fixed heart rate, increased resting heart rate, sinus tachycardia, orthostatic hypotension with systolic blood pressure fall 30 mm Hg or greater, possibly increased susceptibility to silent myocardial ischemia or infarction, reduced circadian rhythm of heart rate and blood pressure, abnormal hormonal regulation to standing and exercise, antibodies to autonomic tissue, denervation hypersensitivity to alpha and beta adrenergic agonists, inadequate increase in heart rate or blood pressure to exercise, reduced left ventricular diastolic filling or ejection fraction, intraoperative cardiovascular instability, corrected QT interval prolongation, and increased QT dispersion. Sensitive and early assessment of CAN is currently possible by means of noninvasive autonomic function tests (AFTs), including time domain and frequency domain indices of HRV, aiming at prevention of the advanced stages. However, a generally accepted standardization of the various test procedures is needed. Despite this problem, it is estimated that CAN can be detected by abnormal AFTs in at least one fourth to one third of people who have type 2 diabetes. In some cases, autonomic dysfunction may be present at the time of manifestation of both type 1 and type 2 diabetes. There is increasing evidence suggesting that the statistical, geometric, frequency domain, and nonlinear measures of 24 hour HRV could be more sensitive and reliable in detecting CAN when compared with AFTs. Moreover, 24 hour recording of HRV provides insights into abnormal patterns of circadian rhythms modulated by sympathovagal activity. Recent studies using cardiac radionuclide imaging techniques have quantified myocardial adrenergic dysinnervation by diminished uptake of the norepinephrine analogs [123I]metaiodobenzylguanidine or [11C]hydroxyephedrine. These methods provide a unique and sensitive tool for direct assessment of the pathophysiology and progression of early sympathetic innervation defects not accessible to indirect autonomic function testing. The prognostic significance of these defects and that of reduced measures of 24 hour HRV in CAN need to be

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determined in large scale prospective clinical trials. 2 figures. 3 tables. 107 references. (AA-M). •

Ulcerative Colitis: A Rational Approach to Management Source: Consultant. 41(4): 541-548. April 1, 2001. Contact: Available from Cliggott Publishing Company. 330 Boston Post Road, Darien, CT 06820-4027. (203) 661-0600. Summary: Ulcerative colitis (UC), a type of inflammatory bowel disease can manifest as proctitis or proctosigmoiditis, left sided colitoss, or pancolitis. This article offers a rational approach to the management of patients with UC. Frequent low volume bowel movements, urgency, rectal bleeding, and tenesmus (ineffective spasms of the rectum) alone suggest proctitis. Prostration, fever, tachycardia (racing heartbeat), dehydration, and complications of blood loss (which may or may not be accompanied by symptoms of proctitis) suggest more severe disease or more extensive bowel involvement. For patients with mild to moderate disease, mesalamine is recommended to induce and maintain remission. Systemic corticosteroids can induce remission in patients with moderate to severe disease but are not useful for maintenance therapy. Azathioprine or 6 mercaptopurine can be used to wean patients with moderate to severe colitis from corticosteroids and to maintain remission. If severe colitis does not respond to corticosteroids, immunosuppressive therapy or colectomy may be needed. Other indications for surgery include development of acute complications related to disease activity and chronic complications, such as dysplasia, carcinoma, recurrent hemorrhage, or growth retardation in children. Annual surveillance colonoscopy with biopsy is recommended for patients with pancolitis and left sided colitis.

Federally Funded Research on Tachycardia The U.S. Government supports a variety of research studies relating to tachycardia. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to tachycardia. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore tachycardia. The following is typical of the type of information found when searching the CRISP database for tachycardia:

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Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

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Project Title: ADENOSINE & KATP CHANNEL CONTROL OF CORONARY BLOOD FLOW Principal Investigator & Institution: Feigl, Eric O.; Professor; Physiology and Biophysics; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 25-MAY-1993; Project End 30-APR-2006 Summary: (provided by applicant): When heart rate increases (as occurs during exercise), coronary blood flow must increase to provide oxygen to the heart to support the augmented myocardial oxygen consumption. The purpose of the proposed research is to discover the essential physiological mechanisms that couple coronary blood flow to myocardial oxygen consumption. Without these mechanisms, the heart becomes ischemic and dies. A new hypothesis, with supporting data, is presented where ATP released from red blood cells in the coronary circulation acts as the mediator of local metabolic coronary vasodilation. A plan is presented to quantitatively test the ATP hypothesis during tachycardia and exercise with a combination of ATP measurements and ATP-receptor blockade. The hypothesis that endothelin vasoconstriction in the outer layers of the left ventricle helps sustain blood flow to the vulnerable inner layers during exercise will be tested with measurements of plasma endothelin levels and endothelin receptor-blocking agents. The postulated role of P-450 enzymes acting on arachidonic acid in the heart to produce extremely powerful coronary vasodilator compounds called EETs and DHETs will be tested with measurements of these compounds and selective blocking agents. The proposed basic research is fundamental to understanding the normal coronary physiology that underlies coronary artery disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: AGE, HYPOTENSIO

EXERCISE,

THERMOGENESIS

AND

POSTPRANDIAL

Principal Investigator & Institution: Seals, Douglas R.; Professor; Integrative Physiology; University of Colorado at Boulder Boulder, Co 80309 Timing: Fiscal Year 2002; Project Start 01-FEB-2000; Project End 31-JAN-2005 Summary: In young adult humans, acute energy intake (feeding) evokes an integrative "postprandial" physiological response which includes an increase in metabolic rate (thermic effect of food intake--TEF) and a number of autonomic nervous system (ANS) and cardiovascular adjustments aimed at providing increased blood flow for digestion (splanchnic vasodilation) while maintaining arterial blood pressure (BP) at preprandial levels. Some older adults with chronic diseases demonstrate a reduced TEF and/or a postprandial fall in BP ("postprandial hypotension"), but it is unknown whether this occurs with age in healthy adults. If the latter is true, some evidence suggests that these changes may not occur with age in adult humans who exercise regularly. The specific aims of the present proposal are to determine if: (1) TEF is lower and postprandial BP declines occur in middle-aged and/or older sedentary adults compared with young adult controls; (2) the lower TEF is due to attenuated postprandial increases in sympathetic nervous system (SNS) activity associated with reduced CNS sympathoexcitatory responsiveness to acute hyperinsulinemia; (3) the postprandial hypotension also is associated with: a) an attenuated or absent whole-limb and skeletal muscle vasoconstriction; b) a smaller reduction in cardiac vagal modulation of heart rate and an attenuated tachycardia; and c) a lower baseline cardiac vagal tone and arterial baroreflex sensitivity; (4) middle-aged and older adults who exercise regularly do not demonstrate the lower TEF and postprandial hypotension observed with age in

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sedentary humans, and whether this is associated with augmented SNS responses, CNS sympathetic responsiveness to circulating insulin, limb vasoconstriction, vagallymediated tachycardia, baseline cardiac vagal tone and baroreflex sensitivity; and (5) the reduced TEF and postprandial hypotension associated with sedentary aging are related to elevated adiposity. Because TEF contributes significantly to daily energy expenditure and, therefore, energy balance, the expected results should provide new and clinically important information concerning the effects of sedentary aging, regular exercise and adiposity on TEF in the context of age-related obesity and its metabolic and cardiovascular co-morbidities. Moreover, postprandial hypotension is associated with post-meal dizziness, weakness, syncope, cerebrovascular ischemia, and angina pectoris. As such, the expected results should provide new insight into the effects of sedentary aging, habitual exercise and body fatness on this clinically-important cardiovascular disorder. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AIRWAY SENSORY NERVES AND DYSPNEA IN HUMAN SUBJECTS Principal Investigator & Institution: Burki, Nausherwan K.; Professor of Medicine; Medicine; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-DEC-2004 Summary: (provided by applicant): Dyspnea, an unpleasant sensation of difficulty in breathing, is a common symptom in patients with cardiopulmonary diseases, but the underlying mechanisms are unclear. Amongst the various neural pathways, unmyelinated vagal C fibers arising from the lungs and airways have been implicated. The long-term objectives are to increase understanding of the mechanisms of dyspnea and specifically the role of pulmonary C fibers. Adenosine is a commonly used therapeutic intravenous drug for treatment of supraventricular tachycardia; it has been frequently reported to cause dyspnea. Recent studies from our laboratory reported the first evidence showing that adenosine stimulates pulmonary C fiber receptors in anesthetized rats. Preliminary human studies from our laboratory indicate that intravenous adenosine causes dyspnea and increase ventilation, and neither affect is associated with bronchoconstriction. Adenosine is known to increase ventilation by stimulating the carotid body chemoreceptors; such reflex stimulation would increase central motor command and could lead to the development of dyspnea. Our hypothesis is that adenosine causes dyspnea by direct activation of pulmonary C fiber, and it is not an indirect effect related to the increase in ventilation. The specific aims of the proposed study are: 1) to determine the latency and magnitude of dyspneic response, change in airway resistance, and ventilatory response to intravenous injection of adenosine in normal subjects and stable asthmatics; 2) to evaluate the effects of pretreatment with theophylline, and adenosine receptor antagonist, on the intensity of dyspnea and the ventilatory effects of intravenous adenosine; 3) to examine whether directly blocking pulmonary C fibers with inhaled lidocaine abolishes the sensation of dyspnea induced by adenosine in these subjects/patients; 4) to investigate if pretreatment with 100 percent O2, by reducing carotid chemoreceptor sensitivity, alters the dyspnogenic and ventilatory effects of intravenous adenosine. These studies should bring a better understanding of the underlying mechanism of adenosine-induced dyspnea and the role of bronchopulmonary C fibers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ANATOMICAL REMODELING AND ELECTRICAL CONDUCTION IN HEART Principal Investigator & Institution: Winslow, Raimond L.; Professor; Biomedical Engineering; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2006 Summary: (provided by applicant): The fiber structure of the heart plays a critical role in shaping electrical propagation. Conduction is influenced by tissue geometric factors such as expansion and contraction, and is anisotropic, with current spread being most rapid in the direction of the fiber long axis. Spatial rate of change of fiber orientation also influences conduction properties. Remodeling of ventricular geometry and fiber organization, including development of interstitial fibrosis, is a prominent feature of several cardiac pathologies, and these alterations may figure importantly in arrhythmogenesis. A detailed knowledge of ventricular fiber structure, how it may be remodeled in cardiac pathology, and the effects of this remodeling on ventricular conduction is therefore of fundamental importance to the understanding of cardiac electro-mechanics in health and disease. We will investigate how anatomical remodeling of ventricular fiber structure influences ventricular conduction, using the canine tachycardia pacing-induced heart failure preparation as a model system. Several aims must be accomplished to do this. First, we will develop MR imaging methods for the rapid reconstruction of ventricular fiber structure. Second, we will use these methods to measure fiber structure in populations of normal and failing hearts. Third, we will develop mathematical methods for identifying statistically significant changes in fiber structure between normal and failing hearts. Fourth, we will measure electrical activation patterns in each heart that is anatomically reconstructed using MR imaging methods. Fifth, we will relate measured changes in fiber structure to measured changes of electrical propagation in each heart using both experimental approaches as well as computational models. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ANTIARRHYTHMIC EFFECTS OF N-3 FATTY ACIDS Principal Investigator & Institution: Mcanulty, John H.; Professor and Head; Medicine; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 01-FEB-1999; Project End 31-JAN-2004 Summary: Ventricular tachycardia (VT) and ventricular fibrillation (VF) are common causes of the 300,000 sudden deaths occurring in the United States each year. Most of these victims have associated heart disease, most commonly coronary artery disease. Populations consuming considerable quantities of fish and marine mammals have lower than expected mortality rates from coronary disease. Interventional and observational trials have indicated that fatty fish consumption decreases the death rate from coronary artery disease, in part by reducing the number of sudden deaths. Animal and tissue culture studies both support the hypothesis that these beneficial effects are from the anti-arrhythmic properties of n-3 long chained polyunsaturated fatty acids (eicosapentaenoic and docosahexaenoic acids). In this prospective, randomized double blinded trial, survivors of VT and VF with an implantable defibrillator will be randomized to supplementation with these n-3 polyunsaturated fatty acids or with a placebo. Adherence to the supplement will be assessed by measurements of plasma, red cell, and adipose tissue n-3 fatty acid concentrations. The primary outcome variable will be the incidence of recurrent VT or VF, but secondary variables will also be assessed using serial ICD assessment, correlation of the rhythms with the biochemical

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measurements of n-3 fatty acids, hospitalization rates and quality of life. The ICD is the best protection available to patients and can store rhythm electrograms which will allow documentation of rhythm endpoints. If the dietary supplementation with n-3 fatty acids demonstrates a reduction of VT and VF in humans at high risk, this would be a stimulus to apply this inexpensive and safe form of treatment to the large populations who are at increased risk of sudden death. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ATRIONODAL BUNDLES:HISTOLOGIC AND PHYSIOLOGIC VALIDATION Principal Investigator & Institution: Racker, Darlene K.; Medicine; Northwestern University Office of Sponsored Research Chicago, Il 60611 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2006 Summary: (provided by applicant): Radiofrequency (RF) catheter ablation of either the "slow" or "fast" AV nodal pathways can cure AV node reentrant tachycardia (AVNRT) and also modify ventricular response to atrial flutter and fibrillation. However, neither the tissues nor mechanisms underlying these arrhythmias are known. Recently, we demonstrated that two separate atrial circuits overlap in the AV junction region: components of the "muscular valvular apparatus", the "circumferential and the perpendicular laminae," which also form the inferior medial atrial wall; and, the collagen encased "multilimb input" to the AVN: the "atrionodal bundles (ABs) and the proximal AV bundle (PAVB)," which is outside of the medial atrial wall epicardium. We showed that each tissue possess unique extracellular (EAP) and transmembrane action potentials (TAP) and transmission properties; EAPs from the atrial and specialized tissues appear side-by-side in traces made at sites where the atrial and specialized tissues overlap; and atrial EAPs and contractions ceased with exposure to high potassium. HYPOTHESIS: A specialized multilimb AVN input with unique histologic and conduction properties is present in human and dog heart. SPECIFIC AIMS are to determine: 1) the position of the ABs and the PAVB in human heart; 2) the myocyte evoking the AB potential and its electrical pathway after iontophoresis of Lucifer Yellow (LY); 3) transmission properties of the ABs during program stimulation of the ABs and SAN by evalulation of the SAN-AB intervals; 4) each ABs role in AVN activation by alterations in the SAN-AVN interval due either to selective ablation of LY-fiUed myofibers or to transection of the AB/PAVB junctions. METHODS: Electrical potentials will be recorded using simultaneous (a) stationary catheter electrodes at the SAN, 3ABs, PAVB, and AVN to monitor electrical coupling, (b) wire electrodes to localize injection and recording sites, responses to photoablation, (c) multielctrode array plaque, (d) 1 percent LY or 3M KCI miropipet electrodes for recording and dye injection using current pulses. Ablations will be made using blue light and scalpel blades. The anatomy, LY pathways, and effects of photoloysis will be evaluated by 3D analysis and reconstructions. Alterations in morphology of electrical potentials, and conduction intervals will be confirmed via timing in the SAN trace and correlation of EAPs and TAPs. These studies are expected to provide a basis for evaluating transmission, arrhythmogenesis, and drug interactions at the tissue level. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CA+2 AND NA+ TRANSPORT AND ARRHYTHMIAS IN HEART FAILURE Principal Investigator & Institution: Bers, Donald M.; Professor and Chairman; Physiology; Loyola University Medical Center Lewis Towers, 13Th Fl Chicago, Il 60611

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Tachycardia

Timing: Fiscal Year 2002; Project Start 05-JUL-2000; Project End 30-JUN-2004 Summary: The goal of these studies is to define the role of altered Ca and Na transport in the development of ventricular tachycardia (VT) in heart failure (HF). We have recently shown that VT in the failing rabbit & human heart initiates by a nonreentrant" mechanism that may be due to triggered activity from delayed afterdepolarizations (DADs) (or early afterdepolarizations, EADs). We also find upregulation of Na/Ca exchange (NaCaX) mRNA, protein and current in HF which could underlie the transient inward current (I-ti) responsible for DADs. We hypothesize that in HF, prolongation of the action potential duration (APD) and increased [Na]1 (due to decreased Na/K ATPase activity) contribute to SR Ca overload and spontaneous SR Ca release. Further, a given SR Ca release in HF will produce greater I-ti (due to increased NaCaX) and larger DADs (due to increased I-ti and reduced 1-K1), resulting in more triggered APs and nonreentrant arrhythmias in HF. Specific Aims will focus on: l. The role of altered APD & ionic currents on both SR Ca load and DAD induction in HF. 2. The alterations in intracellular [Na] and Na/K-ATPase activity & expression in HF. 3. The relationship of SR Ca release to the genesis of arrhythmogenic I- ti's, DADs and triggered APs. 4. The possible contribution of spontaneous SR Ca release to EADs in HF. 5. The effects of blocking Ca influx via NaCaX (with KB-R7943) on E-C coupling, on prevention of I-ti and DADs in myocytes, and on prevention of VT in the intact failing heart in situ. The experimental approaches will include: in vitro patch clamping (voltage, AP & current clamp); fluorescence measurements of [Ca]i and [Na]i; measurement of mRNA & protein (of Ca transporters & Na/K ATPase subunit isoforms) and Na/K ATPase activity; and 3-dimensional cardiac mapping in vivo. Detailed studies in a novel arrhythmogenic rabbit model of nonischemic HF will be extended to include studies in isolated ventricular myocytes from failing and nonfailing human hearts. The results of these studies will provide the foundation for the development of effective therapeutic approaches to modulate nonreentrant initiation of VT and to decrease the high incidence of sudden death in patients with heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CA2+-MEDIATED MECHANISMS OF ATRIAL PACEMAKER ACTIVITY Principal Investigator & Institution: Lipsius, Stephen L.; Physiology; Loyola University Medical Center Lewis Towers, 13Th Fl Chicago, Il 60611 Timing: Fiscal Year 2002; Project Start 01-JUL-2000; Project End 30-JUN-2005 Summary: (adapted from the applicant's description): The long-range goal of the applicant is to understand the physiological mechanisms that determine and regulate atrial pacemaker activity, particularly with respect to latent atrial pacemakers and their contribution to atrial dysfunction. Latent atrial pacemakers are specialized cells localized in specific regions of the right atrium outside of the SA node region. They are thought to participate in a wide variety of atrial arrhythmias including brady-tachy syndrome, atrial tachycardia, supraventricular tachycardia and atrial fibrillation. Although of major clinical importance, the cellular mechanisms underlying latent atrial pacemaker activity are not well understood. Preliminary results by the applicant indicate that latent atrial pacemaker activity is regulated by bursting of local intracellular Ca2+ release, i.e., Ca2+ sparks, from the sarcoplasmic reticulum (SR) specifically during the late phase of diastolic depolarization. The mechanisms governing diastolic release of SR Ca2+ in atrial pacemaker cells is not clear. Whole-cell (perforated & ruptured patch) recording methods and measurements of intracellular Ca2+ concentration ((Ca)i) using laser scanning confocal microscopy will be used to determine

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the mechanism governing diastolic SR Ca2+ release in latent atrial and SA node pacemaker cells isolated from cat right atrium. The following hypotheses will be tested: 1) voltage-dependent activation of T-type Ca2+ current (ICa,T) during the late diastolic slope triggers SR Ca2+ release which in turn stimulates inward Na/Ca exchange current to depolarize the membrane to threshold, 2) both acetylcholine and norepinephrine regulate diastolic SR Ca2+ release triggered by ICa,T and thereby regulate atrial pacemaker activity, 3) by elevating (Ca)i, cardiac glycosides and low extracellular (K) enhance this normal mechanism of atrial pacemaker automaticity, and thereby elicit atrial dysrhythmias not dependent on Ca2+ overload of the SR, 4) low temperature inhibits atrial pacemaker activity by inhibiting diastolic SR Ca2+ release triggered by ICa,T, and 4) transitional atrial pacemaker cells lack diastolic time-dependent currents and therefore depend primarily on SR Ca2+ release triggered by ICa,T for their pacemaker mechanism. It is expected that the results gained from these studies will provide fundamental insight into the cellular mechanisms governing normal and abnormal atrial pacemaker function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CALCIUM IONS: AN INSIGHT TO CARDIAC FIBRILLATION Principal Investigator & Institution: Attin, Mina; None; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-MAY-2002 Summary: (provided by applicant): The objective of this proposal is to investigate the role of calcium (Ca) ions in initiation and maintenance of ventricular fibrillation (VF). This study will provide insight to scientists and clinicians about the mechanism of VF that leads to sudden cardiac death (SCD). Understanding the mechanism of VF is essential for developing new therapies and nursing interventions to prevent and to decrease the incidence of SCD. The specific aims of this study are to: 1) measure intracellular membrane potential while recording the Ca transients; 2) determine the extent to which intracellular membrane potential and the Ca transients are correlated; 3) analyze the spatial distance between membrane potential and the Ca transients, and 4) develop an optical mapping system to permit simultaneous mapping of membrane potential and Ca transients. This study will use the right ventricle (RV) of nine swine during four modes of pacing including regular, incremental, irregular and rapid pacing resembling the rate of ventricular tachycardia and VF. Action potential duration restitution and Ca transients restitution will be constructed for each pacing modes. Pharmacological agents will be given, the effects will be documented and then the agents will be washed out and the effects will be documented again. At each stage of the study, electrical recording will be taken and optical mapping will be performed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CARDIAC CONNEXINS IN IMPULSE PROPAGATION AND ARRHYTHMIAS Principal Investigator & Institution: Jalife, Jose; Professor of Pharmacology; Upstate Medical University Research Administration Syracuse, Ny 13210 Timing: Fiscal Year 2002 Summary: Intercellular communication is essential for normal cardiac impulse propagation. It is thought to be mediated by gap junction channels. Three gap junction proteins, known as connexins (Cxs), are expressed in the heart; these are Cx40, Cx43 and Cx45. However, the specific role of the individual connexins in normal and abnormal

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propagation is unknown. The recent development of connexin knockout mice now makes such knowledge possible. Our overall objective is to investigate the electrophysiological consequences of the absence of specific gap junction channels on impulse propagation in mice lacking either Cx43 or Cx40. We will combine electrocardiographic, microelectrode and patch- clamping techniques, with highresolution microscopic and macroscopic optical recordings of potentiometric dye fluorescence, to measure relevant electrophysiological parameters, which may be affected by Cx43 and Cx40 null mutation. Our Specific Aims are 1. To determine the electrophysiological consequences and pro-arrhythmic effects of reduced intercellular coupling in the ventricles of neonatal homozygote and heterozygote Cx43 knockout mice. We hypothesize that the lack of Cx43 results in a reduction of intercellular communication leading to discontinuous conduction, with an increase in the variability of local conduction times during both sinus rhythm and pacing. Moreover, we surmise that impulse blockade in the homozygote mice will occur preferentially in the direction transverse to fiber orientation and at much slower frequencies than in wildtype or heterozygous mice. 2. To determine the role of Cx40 in impulse propagation in the specialized conducting system, and ventricles of the adult mouse heart. Our hypothesis here is that the null mutation of Cx40 decreases intercellular communication in the specialized conduction system and slows Purkinje fiber conduction velocity, leading to an apparent bundle branch block configuration in the electrocardiogram, and facilitating the induction of reentrant arrhythmias. Further, because of source-sink relationships, we expect that conduction block is more likely to occur at branch points and the Purkinjemuscle than along the Purkinje bundles. 3. To determine the effects of Cx40 null mutation on sinus rhythm and impulse propagation in the atria of the adult mouse heart. Cx40 is expressed in both atria and the sinus node of the mouse. It has been shown that the lack of Cx40 results in P wave prolongation and atrial tachyarrhythmias, including fibrillation. However, in the absence of such arrhythmias, RR interval is unaffected in Cx40-/- mice. We postulate that Cx40 plays a crucial role in intercellular communication in the atria and helps maintain normal intraatrial conduction, but is not essential for synchronized pacemaker discharge in the sinus node. We propose also that the reduction in intercellular communication within the atria of the CX40 knockout mouse is accompanied by an increased susceptibility to reentrant arrhythmias. Overall, the studies proposed are highly significant in that they will provide definite proof or refutation to long-held assumptions regarding the fundamental role of connexins in cardiac electrophysiology and arrhythmias. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CARDIAC IMPULSE INITIATION AND REPOLARIZATION Principal Investigator & Institution: Rosen, Michael R.; Gustavus A. Pfeiffer Professor of Pharma; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2002 Summary: The general hypothesis for this Project is that sympathetic innervation contributes importantly to the changes in ion channels that occur developmentally and to the evolution of specific receptor-effector pathways. We hypothesize as well that in the setting of incomplete sympathetic innervation abnormalities of specific ion channels and signal transduction pathways set the stage for lethal arrhythmias. This hypothesis derives from our earlier work on both beta-and alpha-adrenergic signaling and developmental changes in electrophysiology in the normal canine, rat and rabbit heart. We now focus on two canine models of disordered innervation: (a) surgical interruption of the sympathetic nerves to the heart in the first 24 hours of life, and (b) familial failure

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of innervation to a portion of the anteroseptal left ventricle in Germ Shepherd Dogs. Important, surgical right stellectomy and thoracic sympathectomy is characterized by asystolic sudden death in the first weeks of life; whereas the familial failure of innervation results in ventricular tachycardia and sudden death at 4-5 months of life. We perform intact animal, isolated tissue and single myocyte experiments to study the electrophysiology (focussing on repolarization and impulse initiation), ionic currents (focussing initially on I/ks and I/kr), signal transduction (focussing on beta-receptors, G proteins and adenylate cyclase) and molecular physiology (focusing initially on mRNA for canine ERG and on KvLQT1 and minK), with a view towards working vertically from the ECG of the intact animal through the molecular mechanisms responsible for arrhythmic events. Moreover, in cooperation with all other Projects on the Program, we shall achieve an understanding of the relationship between nerve-myocyte interaction, evolution of signaling processes and evolution of electrophysiologic control mechanisms. The significance of the proposed research is that it not only utilizes multiple approaches in an attempt to understand the control of rhythm and arrhythmias in the proposed models, but the models, themselves, incorporate features important clinically, in that they are relevant to pause-dependent tachycardias, those triggered by delayed after depolarizations, and to catecholamine-or exercise-dependent tachycardias that tend to afflict otherwise healthy young individuals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CARDIOVASCULAR DISEASE MECHANISMS IN SLEEP APNEA Principal Investigator & Institution: Somers, Virend K.; Professor; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 29-FEB-2004 Summary: Obstructive sleep apnea is emerging as an important risk factor for hypertension, heart failure, and ischemic heart disease. The mechanisms linking obstructive sleep apnea to cardiac and vascular disease are poorly understood. Utilizing recent developments in neural circulatory control and in vascular biology, we have acquired exciting preliminary data that promise mechanistic insight into the association between sleep apnea and cardiovascular disease. These data suggest that patients with sleep apnea have: 1) increased sympathetic neural traffic, tachycardia, and marked impairment of heart rate and blood pressure variability; 2) impaired endothelial vasodilator function; 3) dramatic overnight increases in endothelin and cytokines, with reductions in both after acute continuous positive airway pressure (CPAP) therapy; and 4) a reduction in blood pressure and sympathetic drive after long-term CPAP therapy. These interesting findings have led us to propose the overall hypothesis that obstructive sleep apnea is associated with neural, vasoactive and inflammatory abnormalities, which may be implicated in cardiovascular dysfunction, and that these abnormalities are attenuated by long-term therapy with CPAP. We will test the following specific hypotheses: 1) That patients with sleep apnea have impaired neural mechanisms regulating circulatory control. 2) That patients with sleep apnea have impaired endothelial function, and increased production of endothelin, cytokines and leukocyte adhesion molecules. 3) That long term effective therapy with CPAP improves cardiovascular function by attenuation of these abnormalities in neural, vasoactive and inflammatory mechanisms. An important and novel strength of these studies is that the integrity of the hypotheses will be tested with careful exclusion of potential confounding variables such as obesity, hypertension, left ventricular dysfunction, exercise capacity and impaired glucose tolerance. This proposal builds on our broad experience in studies of both sleep apnea and neural circulatory control, and should

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contribute to the understanding and treatment of cardiac and vascular disease in patients with obstructive sleep apnea. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHAOS AND CARDIAC ARRHYTHMIAS Principal Investigator & Institution: Garfinkel, Alan J.; Associate Professor; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002 Summary: Multiple circulating wavefronts in an excitable medium produced by computer simulations are an example of spatio-temporal chaos. Their close similarity to experimentally-recorded activation patterns during atrial or ventricular fibrillation suggest that fibrillation may also be a form of spatio-temporal chaos, and raises the possibility that recently-developed chaos control strategies can be applied to fibrillation. We have previously shown that a pacing algorithm based on chaos control theory could successfully regularize a chaotic ventricular tachycardia induced by ouabain in isolated rabbit ventricle. The major objective of this project is to determine whether a similar strategy can be developed for ventricular fibrillation. We have modified the van Capelle & Durrer computer model of propagation in a two-dimensional excitable lattice, and have shown that multiple circulating wavefronts (spiral waves) simulating fibrillation can be induced. Local site recordings show clear evidence of chaotic behavior, and exhibit the dynamic features (fixed point and stable and unstable manifolds) necessary to apply the OGY chaos control method, which we successfully applied to the chaotic ouabain-induced arrhythmia. The model closely simulates the behavior of circulating reentrant wavefronts in the in vitro canine epicardial slice preparation described in Project 2, which also shows evidence of chaos at local recording sites. Criteria for detecting spatio-temporal chaos at individual elements in the lattice (equivalent to the information that could be obtained from a local intracardiac electrogram) will be developed in the van Capelle & Durrer model, and this information used develop a perturbation strategy based on chaos control theory (analogous to pacing at a one or more sites in the lattice) to determine whether local and global chaos control can be achieved. The results of computer simulations will be directly validated experimentally using the in vitro canine epicardial slice preparation and, if successful, adapted to the in vivo fibrillating canine heart. A second objective of the project is to further understand and improve the chaos control pacing algorithm which we have previously successfully applied to ouabain-induced ventricular tachycardia in the rabbit interventricular septum, a less spatially complex chaotic cardiac arrhythmia. Using high resolution activation mapping with extracellular electrodes, the ouabain-induced arrhythmia will be mapped to evaluate its mechanism and spatial properties, and to gain insight into the mechanism by which the chaos control pacing algorithm is effective. Improvements to our current chaos control algorithm will be further developed and tested in the septal preparation. These improvements to the chaos control pacing algorithm in the ouabaininduced arrhythmia will be essential for chaos control pacing algorithms designed for fibrillation. Ultimately, the goal is to develop an intelligent pacing strategy based on chaos control theory which will either terminate fibrillation or significantly decrease the defibrillation threshold. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CHRONIC MONITORING OF ISCHEMIC MODELS OF SUDDEN DEATH Principal Investigator & Institution: Smith, William M.; Professor; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2003 Summary: Most sudden cardiac death (SCD) is associated with coronary artery disease, but little is known about the exact sequence of events that leads up to it and the mechanisms responsible for it. There is a complex interplay between old myocardial infarcts, acute ischemia, the status of the autonomic system, mechanical viability, and electrophysiology that leads to SCD and influences whether tachycardia or bardycardia is the final rhythm. In this project, it is proposed to combine a unique set of technological and physiological resources to study the events surrounding sudden death. An animal model of infarct/ischemia leading to spontaneous SCD has been developing and will be studied in two complementary ways. One set of animals will be instrumented with a custom-developed telemetry system to acquire electrophysiologic and functional data during the conscious, ambulatory state, eliminating the confounding effects of thoracotomy and anesthesia and anesthesia on the incidence and nature of sudden death. Another set of animals will be studied with high resolution, three dimensional mapping to elucidate the mechanisms of the spontaneous arrhythmias that lead to SCD. It is hypothesized that the balance between the vagal and sympathetic arms of the autonomic system and that changes in repolarization properties of the myocardium are predictors of which animals die suddenly and spontaneously and spontaneously as well as the mode of death. It is also hypothesized that spontaneous tachycardia/fibrillation is initially reentrant and that the old infarct is involved in the arrhythmia maintenance. Further, it is hypothesized that bradycardia is associated with pump failure rather than a vagal reflex leading to hypotension. It is proposed to use the data from this research to develop, implement and validate measures that predict imminent SCD on the time scale of seconds to minutes. Because of the continuous nature of data acquisition over several days when no sustained arrhythmias are observed, it will be possible to determine the specificity as well as the sensitivity of derived predictors. Innovations in telemetry capability, cardiac mapping, and new animal models of spontaneous sudden cardiac death will provide information about the context and mechanisms of sudden death that has not been available before. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SYNDROME

CIRCULATORY

DYSFUNCTION

IN

CHRONIC

FATIGUE

Principal Investigator & Institution: Stewart, Julian M.; Professor; Pediatrics; New York Medical College Valhalla, Ny 10595 Timing: Fiscal Year 2002; Project Start 24-AUG-2001; Project End 31-JUL-2005 Summary: Chronic fatigue syndrome (CFS) is associated with orthostatic intolerance which often takes the form of postural orthostatic tachycardia syndrome (POTS) in adolescents. Preliminary data suggest the novel concept that defective vasoconstriction produces POTS in CFS with cardiac autonomic changes as a secondary response. CFS patients will be compared to healthy controls and to controls with simple faints to test 3 hypotheses: 1) Blood is redistributed peripherally and redistribution is enhanced during orthostasis producing increased microvascular filtration and dependent edema. Central hypovolemia causes decreased cardiac output, reflex tachycardia and reduced cerebral blood flow. This is enhanced during orthostasis producing increased microvascular

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filtration, dependent edema, and peripheral pooling. These changes alter the interstitium, and cause reflex tachycardia, reduced cerebral blood flow and often hypotension. Blood volume and cardiac output using the indocyanine green dye dilution technique will be measured supine, during conventional 700 head-up tilt, and during low angle head-up tilt. Cerebral blood flow velocity (CBFv) will be estimated by transcranial Doppler ultrasonography. Thoracic, splanchnic, and pelvic vascular volumes will be measured by impedance plethysmography, and limb blood flow, arterial flow, venous volume-pressure relation, and venous pressure will be measured by venous occlusion strain gauge plethysmography. These will show increased blood flow to lower extremities when upright. Central hypovolemia will occur and will reduce CBF and produce symptoms of CFS. Cardiac autonomic status including baroreflex will be assessed by heart rate and blood pressure variability and transfer function. Baroreflex and heart rate variability will be decreased and blood pressure variability will be increased related to circulatory deficit 2) The defect in vasoconstriction is heterogeneous comprising abnormal arterial baroreflex mediated sympathetic vasoconstriction in one subgroup of CFS patients and abnormal local vasoconstriction in a second subgroup with defective veno-arteriolar reflex (arterial baroreflex insensitive dysfunction). Low angle tilt will be used to activate baroreflex mediated and local reflexes. Local reflexes including myogenic, metabolic and veno-arteriolar will be sorted out through use of supine testing designed to specifically stimulate a specific reflex (limb hang, large pressure step and reactive hyperemia) and measuring peripheral resistance. 3) Cardiac autonomic findings are secondary to circulatory changes. Thus, tachycardia relates to vagal withdrawal because of circulatory insufficiency. CFS patients will be treated with midodrine or placebo in a cross-over study. Using supine and low angle tilt experiments, circulatory measurements and psychological instruments will be combined to demonstrate that circulatory abnormalities, autonomic abnormalities and symptoms correct in a subgroup of CFS patients with low resting peripheral resistance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SYNDROME

CLONIDINE

TREATMENT

FOR

NEONATAL

ABSTINENCE

Principal Investigator & Institution: Gauda, Estelle B.; Associate Professor; Pediatrics; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2006 Summary: (provided by applicant): In the United States, as many as 20,000 babies a year are born to opioid ("narcotic") addicted mothers. Like their mothers, these infants are opioid dependent. Following birth, the infant is removed from its opioid source, inducing a withdrawal syndrome in these infants. Withdrawal symptoms in newborns include vomiting, diarrhea, poor feeding, tachycardia, hypertension, diaphoresis, restlessness, insomnia, irritability, tremors, clonus, hyperphagia with poor growth and acidosis, reversible neurologic abnormalities, and even seizures. This complex of signs and symptoms is referred to as neonatal abstinence syndrome (NAS). Reinstitution of opioids followed by a slow tapering protocol is currently the standard of care, necessitating prolonged hospitalization from weeks to months. Clonidine is a nonnarcotic central alpha2-adrenergic receptor agonist that blocks the effects of overexcitation of the sympathetic nervous system and is an approved treatment for opioid withdrawal in adults. We currently have a physician sponsored IND (#63,781) to study the effect of clonidine as adjunct therapy to opioids for the treatment of NAS. This proposal will test the hypothesis that combination therapy of clonidine and opioids is 1) safe and efficacious, 2) allows reduced amount of opioid drug use, and 3) results in

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shorter time of treatment and hospitalization. This will be accomplished in a randomized, placebo controlled double blind clinical trial comparing diluted tincture of opium (DTO) combined with a placebo (control) vs. DTO combined with clonidine. Additional sub-studies include determination of 1) pharmacokinetics and pharmacodynamics of DTO and clonidine in the enrolled cohort and 2) further safety evaluation by evaluating developmental outcome on the Bayley Scale of Infant Development (BSID) at 6 and 12 months of age. Pharmacokinetics will be determined by measuring serum concentrations of clonidine and morphine and analyzing volume of distribution, elimination half-life and clearance. These results will have important clinical implications and may change the standards of care not only for management of infants with severe NAS, but also for the management of infants and children, after long-term iatrogenic opioid exposure for instance following prolonged analgesia for mechanical ventilation or multiple operations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COMPREHENSIVE DIAGNOSIS OF ISCHEMIC HEART DISEASE BY MRI Principal Investigator & Institution: Yang, Phillip C.; Medicine; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2005 Summary: A new real-time, interactive cardiac magnetic resonance imaging system (RTIS) has been developed. The RTIS allows continuous dynamic acquisition, interactive selection of any scan plane, and real-time image display at 16 frames/second (6 complete images/second) without cardiac gating or respiratory breath-holding. A clinical trial of the RTIS demonstrates that the system provides clinically reliable evaluation of LV function. The goal of this proposal is to use the RTIS technology to develop a new imaging protocol for a comprehensive diagnosis of ischemic heart disease. The RTIS platform will be augmented by imaging sequences for coronary artery, stress-induced wall motion, and myocardial perfusion. The first phase will focus on optimizing each imaging sequence. Each optimization will be validated by systematic comparison to the respective diagnostic gold standard. High-resolution coronary artery imaging sequence will allow immediate screening, localization, and visualization of the desired coronary artery. Frame rate of 30 complete images/second will provide imaging of stress induced wall-motion in tachycardia range. Cardiac-gated single shot imaging will enable rapid acquisition of several frames per systole over multiple planes to cover the entire heart for first- pass perfusion imaging. The second phase will consist of a prospective clinical trial of each optimized sequence. During the final phase, the 3 imaging sequences will be integrated seamlessly into the RTIS to test the clinical utility of a rapid and robust comprehensive cardiovascular diagnostic system (CVMR). The wide range of tissue contrast mechanism of MRI creates a huge potential in cardiovascular imaging. Robust imaging sequences have been developed to display physiologic parameters to diagnose cardiac ischemia. The major thrust of this research plan is to develop an advanced, integrated imaging system to test the hypothesis whether such comprehensive approach will enhance non-invasive diagnosis of ischemic heart disease. The final product will be a diagnostic system that maximizes the MR tissue contrast properties coupled with real-time interactive capabilities and easy, intuitive user-interface. The CVMR will demonstrate optimal transfer of innovative technology to cardiovascular medicine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: COMPUTER MODEL OF THE CANINE VENTRICLE Principal Investigator & Institution: Gilmour, Robert F.; Professor of Physiology; Biomedical Sciences; Cornell University Ithaca Office of Sponsored Programs Ithaca, Ny 14853 Timing: Fiscal Year 2004; Project Start 15-DEC-2003; Project End 30-NOV-2007 Summary: (provided by applicant): Sudden death secondary to ventricular fibrillation (VF) remains a leading cause of mortality in the US. Therapy for VF has been largely ineffectual, principally because the underlying mechanisms for VF are not well understood and probing for potential mechanisms has been hindered by the inability to precisely modify specific ionic currents. To address these issues, we propose to develop a data-driven computer model of the electrical behavior of the canine ventricle. Specifically, we will: 1) Experimentally characterize IKr, ICa, IK1, INaCa, and the late sodium current INa in myocytes obtained from specific regions of the ventricles. These particular currents will be studied because they play a significant role in repolarization. They will be measured using action potentials recorded at rapid pacing rates as the command waveforms, to replicate current behavior during a tachyarrhythmias. 2) Develop deterministic Hodgkin-Huxley and Markov models for each ionic current for each anatomical region using the time series and steady state current data obtained under Specific Aim 1. Optimization routines will be used to determine unknown parameters in the models by comparing the model current to experimental data. 3) Incorporate the models of the individual currents into computer models of regionspecific single canine ventricular myocytes. Models of left and right ventricular epicardial, midmyocardial and endocardial myocytes of basal and apical origin and of right and left ventricular Purkinje myocytes will be developed. 4) Incorporate the single cell models into a 3-D computer model of the canine ventricle using a modified version of the phase field method. The model will be written using a portable parallel version of the code and run on a parallel computer and multi-node clusters. Initially, the model will consist of the left ventricle, with epicardial, midmyocardial and endocardial layers. More detailed anatomical models subsequently will be constructed to include the HisPurkinje system and the right ventricle. 5) Use the 3-D model to test candidate hypotheses for the development of VF. The initial test will determine whether suppressing dynamic electrical heterogeneity prevents VF. The computer model of ventricular electrical function we propose will provide an invaluable tool for drug discovery and the evaluation of algorithms for anti-tachycardia and anti-fibrillatory pacing and defibrillation. As such, the model is expected to have a significant impact on the diagnosis and treatment of lethal heart rhythm disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CORE--ANIMAL MODEL AND CELL Principal Investigator & Institution: Kass, David A.; Professor; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002 Summary: 1. Purpose, Core C, the animal model and cell isolation core, provides support for the central animal model used by Projects 1-4. This includes expert surgical instrumentation, follow-up care, and isolation of viable cardiomyocytes from several layers of the left ventricle. Myocytes are employed in projects 1-3 for molecular dissection of potassium and calcium channel physiology in normal and failing hearts. Myocytes are utilized in Project 4 for the purpose of studying neurohormonal modulation of ion channels in normal and failing hearts, and test the role of an altered

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extracellular matrix environment. Chunk tissues are also provided by Core C at time of animal sacrifice and are used for a variety of molecular assays and histochemical analyses. Two models are employed in Core C, the standard 4 week tachycardia-pacing model of dilated cardiomyopathy, and an accelerated model employing combined neurohumoral activation with relatively short-term tachycardia pacing (Project 4). The major roles of the core are 1) to provide a weekly supply of acutely isolated myocytes from control and abnormal (failing) left ventricles; 2) to provide a standardized hemodynamic/organ electrophysiologic characterization of hearts from which these cells are obtained; 3) to provide chronic surgery-instrumentation and post operative care for animals requiring chronic repetitive conscious hemodynamic assessment; and 4) to provide all required medical records for chronic care and animal maintenance, and to administer these protocols following policies set forth by the Animal Care and Use Policies of the Johns Hopkins University pursuant to guidelines established by the National Institute of Health. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CX43 IN A GENETIC MODEL OF ALTERED MYOCARDIAL CONDUCTION Principal Investigator & Institution: Saffitz, Jeffrey E.; Professor of Pathology & Immunology; Pathology and Immunology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-APR-1998; Project End 31-MAY-2005 Summary: The goal of the proposed research is to define the functional role of Cx43 in normal cardiac conduction and to delineate the role of altered coupling at gap junctions in the pathogenesis of conduction disturbances and arrhythmias. Proposed experiments will be performed using mice that are heterozygous for a null allele for the gene encoding the major cardiac gap junction protein, Cx43 (Cx43 plus/minus mice). These mice produce 50 percent of the wildtype level of Cx43 and have significant reduction in the number of gap junction interconnecting ventricular myocytes. The functional consequence of reduced Cx43 expression in adult mice is a 25-30 percent slowing of ventricular conduction velocity. Whereas the electrophysiological phenotype in Cx43 plus/minus mice is subtle under physiological conditions, a more dramatic phenotype can be elicited under pathophysiological condition. In response to acute regional ischemia, Cx43 plus/minus mice exhibit accelerated onset and increased incidence, frequency and duration of ventricular arrhythmias. The proposed research is focused on defining mechanisms by which reduced coupling promotes arrhythmias in accute and chronic ischemic heart disease. Studies in Specific Aim 1 will elucidate the mechanistic relationship between the rate and extent of electrical uncoupling at gap junctions and development of ventricular tachyarrhythmias induced by acute ischemia. Studies in Specific Aim 2 will define arrhythmia mechanisms in Cx43 plus/minus following acute coronary occlusion and delineate the roles of Cx43 and altered cell-to- cell coupling in electrical triggering events and sustained conduction abnormalities that underlie initiation and maintenance of ventricular arrhythmias in the setting of acute myocardial ischemia. In Specific Aim 3, the role of gap junction remodeling in the pathogenesis of arrhythmias in chronic ischemic heart disease will be elucidated by comparing arrhythmogenesis in Cx43 plus/minus and wildtype mice with healed myocardial infarcts. And in Specific Aim 4, molecular and structural determinants of conduction will be delineated using neonatal mouse ventricular myocytes grown in patterned arrays of defined structure and packing geometry, and analyzed by high resolution optical mapping. The results of the proposed research will define mechanisms by which

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reduced coupling promotes ventricular tachyarrhythmias in mouse models of acute and chronic ischemic heart disease in patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CYTOKINE-INDUCED ARRHYTHMIAS IN CONGESTIVE HEART FAILURE Principal Investigator & Institution: London, Barry; Associate Professor of Medicine; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 28-FEB-2005 Summary: (the applicant's description verbatim): Arrhythmias are a major health problem in cardiomyopathies of both ischemic and non-ischemic origin. As many as 50 percent of patients with congestive heart failure (CHF) die suddenly, accounting for more than 250,000 annual deaths. Pharmacological treatments of arrhythmias often fail, and internal defibrillators are expensive and limit quality of life. Inflammatory cytokines, including TNF-alpha, are increased in the serum and hearts of patients with CHF. TNF-alpha is also transiently increased following myocardial infarction, is elevated in inflammatory conditions such as sepsis, and increases with age and hypertrophy. All of these conditions are characterized by increased susceptibility to ventricular arrhythmias. The potential role of cytokines in the pathogenesis of arrhythmias has not been extensively studied. We have recently engineered mice that overexpress TNF-alpha in the heart and develop a cardiomyopathy characterized by atrial and ventricular dilatation, decreased ejection fraction, CHF, and decreased survival. Radio-telemetry monitoring of transgenic mice shows high-grade atrial and ventricular arrhythmias. Optical mapping studies of program-stimulated, Langendorffperfused hearts using voltage- and Ca2+-sensitive dyes show inducible ventricular tachycardia (VT), slow conduction of premature beats, elevated diastolic and decreased peak systolic Ca2+, and prolongation of the Ca2+ transient. Mating of these mice to long QT transgenic mice yields offspring that die suddenly, without evidence of CHF. The goals of this project are to determine the mechanism(s) by which cytokines may promote arrhythmias and sudden death in acute and chronic cardiac conditions, and to test whether treatments for CHF reverse the effects. To this end, we will study ambulatory telemetry-monitored mice, isolated Langendorff-perfused hearts stained with voltageand Ca2+-sensitive dyes, and isolated myocytes from control and transgenic mice. We will: 1) Test the hypothesis that acute exposure to TNF-alpha, IL-1 beta, and/or LPS predisposes to cardiac arrhythmias, and determine the mechanism(s) responsible; 2) Identify the mechanisms responsible for atrial and ventricular arrhythmias in the TNFalpha mouse model of CHF. 3) Determine to what extent and by what mechanisms treatments of CHF with beta-blockers, ACE inhibitors, and soluble TNF receptors decrease arrhythmias; and 4) Examine to what extent and by what mechanisms repolarization abnormalities exacerbate arrhythmias and sudden death in this mouse model of CHF. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DATA COORDINATING CENTER FOR SCD IN HEART FAILURE TRIAL Principal Investigator & Institution: Lee, Kerry L.; Associate Professor of Biostatistics; Community and Family Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 01-MAY-1997; Project End 30-APR-2003

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Summary: The objective of this proposal is to establish the Statistical and Data Coordinating Center for the multicenter randomized clinical trial of prophylactic amiodarone or implantable defibrillator therapy vs. Conventional heart failure therapy in patients with Class II or Class III congestive heart failure (CHF) and an ejection fraction less than or equal to 35%. Qualifying patents (n=2,500) will be randomized in equal proportions to three treatments: conventional CHF therapy and placebo (control arm); conventional therapy combined with the use of amiodarone; and conventional therapy combined with a single lead, pectoral ICD that can be inserted on an outpatient basis. After discharge, all patients will be followed via clinic visits at 1 week, 4 weeks, 3 months, and every 3 months thereafter. Patients will be recruited over a period of 2.5 years, with a subsequent minimum follow-up of 2.5 years. The primary endpoint of the trial is all-cause mortality. Secondary endpoints include: 1) cardiac mortality and arrhythmic mortality; 2) ventricular tachycardia/fibrillation and bradyarrhythmias assessed via the ICD memory log; 3) morbidity; 4) quality of life; and 5) cost of care and cost effectiveness. In collaboration with the Clinical Coordinating Center (CCC) and the Economics and Quality of Life Center, the Data Coordinating Center will perform the following major functions: 1) participate in all phases of study planning; 2) coordinate the preparation of data collection forms; 3) prepare a manual of operations; 4) provide training/guidance in data collection procedures; 5) coordinate the randomization of patients; 6) organize the flow and management of all patient data; 7) establish high standards of quality control for data management; 8) perform on-site monitoring of completed data forms; 9) prepare regular status reports for the CCC and for all study committees; 10) dispense payments to clinical sites for enrolling and following patients; 11) perform appropriate statistical analyses of study data; and 12) participate in the preparation of study publications. Noteworthy features of this proposal include: a detailed assessment of sample size requirements; telephone randomization of patients; double data entry; on-site audits of data; economical and efficient computer hardware and software; state-of-the-art methods of data analysis; and an experienced team of investigators. Through the services it provides, the Data Coordinating Center will be a vital resource in the execution of this clinical trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DECOUPLING DYNAMICS OF THE AUTONOMIC NERVOUS SYSTEM Principal Investigator & Institution: Chon, Ki H.; Biomedical Engineering; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2006 Summary: (provided by applicant): The purpose of this R21 proposal is the development of a new nonlinear method that will be able to separate the dynamics of the sympathetic and parasympathetic nervous activities from noninvasive recordings of heart rate data. The cardiac autonomic nervous system (ANS) is an especially important control system that is responsible for maintaining [proper homeostasis of the cardiovascular system. Clinically-reliable assessment of the state of the ANS requires accurate nonlinear techniques that can separate the dynamics of sympathetic and parasympathetic nervous activities. Decoupling the dynamics of the two autonomic nervous activities based on heart rate data is important because it can be used as a powerful non-invasive marker for determining the state of the ANS balance. Experimental evidence suggests that myocardial infarction, chronic heart failure, ventricular tachycardia, and sudden cardiac death all exhibit signs of ANS imbalance. Currently, there is no method that can accurately characterize dynamics of the two branches of ANS using noninvasive

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approaches. One of the current standards in assessing the balance between the sympathetic and parasympathetic nervous systems is to compute the ratio of the low frequency (LF) to high frequency (HF) power obtained from spectral analyses of the heart rate data. The LF/HF ratio is inaccurate because it does not truly reflect the balance between the two branches of ANS activities, and is a linear approach despite the fact that the ANS involves nonlinear control. Consequently, characterization of the ANS using linear power spectra of the heart rate data may limit identification of subtle changes in dynamics from healthy to diseased states, for example. Preliminary results based on a limited database of healthy subjects suggest that our method is able to separate dynamics of the two ANS activities. The first aim of the R21 proposal is to further develop, modify, and enhance the capability of the method as the technique is applied to an existing clinical database to validate the efficacy of the approach. The second aim is to detect, quantify, and Interpret differences in dynamic characteristics of the ANS between normal and diseased subjects, in an attempt to find a marker for increased risk of sudden cardiac death. The final aim is to disseminate the developed software to the 9iomedical engineering community via the internet so that the algorithm can be tested with other researchers' own databases. Identifying and quantifying differences in the dynamic characteristics of ANS between normal and diseased conditions may lead to a better understanding of the role of the autonomic function imbalance in diseased conditions, and should have important clinical diagnostic and prognostic applications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DETERMINANTS OF CATHETER ABLATION FAILURE Principal Investigator & Institution: Po, Sunny S.; Medicine; University of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 73126 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 30-NOV-2007 Summary: (provided by the applicant): The long-term objective of this project is to identify the determinants of catheter ablation failure in AV nodal reentrant tachycardia (AVNNRT) and accessory pathways (AP). Recently, the NASPE Catheter Ablation Registry showed that despite all the advances in mapping and ablation technology, the success rate of ablation has not improved between 1993 and 1998, suggesting that new strategies for selecting the ablation target are needed. The Specific Aim 1 of this project is to elucidate the causes of failed AP ablations. We hypothesize that the main cause of failure in AP ablation is inaccurate localization of the AP when the AP has an oblique course. We will test this hypothesis by reversing the activation wavefront using two different pacing sites to help identify an isolated AP potential, which will be targeted for ablation. The Specific Aim 2 of this project is to elucidate the causes of failed AVNRT ablations. We postulate that the main cause of failed AVNRT ablation is that the reentrant circuit in AVNRT is not well understood. Our working hypothesis is that identification of the reentrant circuit and atrial connections in AVNRT will facilitate appropriate target selection and improve success in AVNRT ablation. We will systemically examine the reentrant circuit by (1) map the earliest retrograde atrial activation to help identify the retrograde limb of the circuit in each variant of AVNRT. (2) establish the presence or absence of a lower common pathway in each variant of AVNRT to help localize the circuit. (3) deliver late atrial extrastimuli at different sites to identify the antegrade limb of the circuit. (4) ablate the reentrant circuit based on the mapping result to further confirm the location of the circuit. My past research has focused on basic electrophysiology (ion channel related research). My immediate career goal is to utilize this project to successfully change my research direction from basic to

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clinical electrophysiology. My long-term goal is to be a "linker" between basic and clinical electrophysiology and continue exploring the mechanism of cardiac arrhythmia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DOES VT BEGET VT? REMODELING IN HEALED INFARCTION Principal Investigator & Institution: Callans, David; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-AUG-2004 Summary: Protracted atrial fibrillation (AF) conditions the atrium through electrical remodeling to perpetuate AF (AF begets AF). Whether this is true for episodic ventricular tachycardia (VT) due to healed myocardial infarction (MI) is not known so this proposal asks whether VT begets VT. A related issue is how VT electrically remodels the infarcted ventricle. Experimental and clinical evidence indicates that postNG VT is reentrant. While VT maintenance mechanisms are controversial, the role of refractoriness in VT initiation is usually not disputed. We therefore propose to study whether episodic VT affects VT inducibility and remodels refractoriness. Study hypotheses were based on the distinct properties of the infarcted (1Z), border (13Z), and normal (NZ) zone tissues associated with MI and on the phenomena of repolarization remodeling due to cardiac memory, failure or hypertrophy. Hypothesis 1 is that VT remodels refractoriness even in hearts already remodeled by MI. Hypothesis 2 is that refractoriness remodeling in the IZ, BZ and NZ differentially responds to the influence of VT rate versus site of origin. Hypothesis 3 is that VT-dependent changes in inducibility result from differences in refractoriness remodeling of the BZ with respect to the IZ or to the NZ. Hypothesis 4 is that changes in BZ and NZ plateau and repolarization currents are responsible for refractoriness remodeling in these tissues. To test these hypotheses we will use swine having healed MI caused by bead embolization. Fast or slow ventricular pacing (VP) from 1 of 3 test sites will simulate episodic VT. VT inducibility and peri-infarct endocardial refractoriness; will be assessed in vivo using CARTO electro-anatomic catheter mapping before and after MI and after VP of MI. Terminal in vitro studies will use whole cell voltage clamp to correlate remodeled BZ and NZ refractoriness with changes in plateau ion currents. We will measure steady state, peak activated and kinetic properties of Ik and ICaL and the current-voltage relations of Ik1 and InaCa. Indo-1 and fluo-3 recordings of the calcium transient will be used to determine the direction and relative magnitude of InaCa flux. Refractoriness due to INa reactivation will be detected via voltage and time-dependent recovery of upstroke velocity. If the study hypotheses are true then the labile and inhomogeneous remodeling properties of the post-MI heart may cause episodic VT to have either a positive or negative effect on VT inducibility. If the latter occurs then novel therapy based on pacing may be possible. If the former is true then preventive therapy could be directed against such remodeling. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DUAL GENE THERAPY FOR HEART FAILURE Principal Investigator & Institution: Nuss, H B.; Medicine; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-AUG-2004 Summary: Heart failure is a multifactorial disease, having both electrical and contractile components. Downregulation of key potassium channels and concomitant prolongation and instability of repolarization, predispose the heart to arrhythmias. Meanwhile,

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downregulation of the sarcoplasmic reticulurn Ca2+ ATPase and concomitant calcium handling abnormalities contribute to depressed myocardial contractility. The electrical abnormalities and the contractile abnormalities are not mutually exclusive. Alterations in the control of membrane voltage will modulate the triggered release of Ca2+ from the sarcoplasmic reticulurn and, conversely, alterations in the intracellular calcium transient will influence membrane potential. It is the interplay between the electrical and contractile abnormalities of heart failure which compounds the complexity of abnormalities and confounds the design of successful treatments. Novel antiarrhythmic gene therapy based upon manipulation of a select K channel gene alone to decrease susceptibility to arrhythmias may lead to depressed contractility, which is already depressed in heart failure. Conversely, genetic manipulation of a SR Ca2+ ATPase protein alone, to amplify contractility, may create a proarrhythmic substrate in a failing heart which is already predisposed to fatal arrhythmic events. Thus, monogenic strategies, based upon selective overexpression of a single gene, may not suffice to correct heart failure abnormalities because of the interplay between excitation and contraction in cardiac muscle. This proposal seeks to offset abnormalities of tachycardia, pacing- induced heart failure in rabbits using combination gene therapy: overexpression of a select K channel gene and a SR Ca2+ ATPase gene in tandem. As a prelude we will test the hypotheses that gene therapy targeted to correct the electrical abnormalities alone or the calcium handling abnormalities alone will result in adverse conditions. The proposal focuses on potassium channels and SR Ca2+ ATPase's that are highly relevant to repolarization and contractility in the human heart failure. In vivo adenoviral mediated gene transfer, cellular and cardiac electrophysiology, and quantitative modeling will be used to investigate repolarization and calcium handling with the goal of correcting the electrical and contractile abnormalities in heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECTS OF ETHANOL ON CARDIAC NEUROENDOCRINE DEVELOPMENT Principal Investigator & Institution: Mckenzie, James C.; Howard University Washington, Dc 20059 Timing: Fiscal Year 2002 Summary: Fetal Alcohol Syndrome (FAS) consists of a constellation of pathologies and functional/development abnormalities resulting from alcohol exposure in the womb. Medical problems related to FAS include retarded body and mental development, craniofacial abnormalties and cardiac structural and functional deficits. Some of these abnormalities appear due to alcohol-induced death of neural crest cells which migrate fromthe developing nervous system and give rise to structual and functional components of many organ systems, including the autonomic nervous system. It is hypothesized that underpopulation of the cardiac parasympathetic intrinsic nervous system may result from cell death and insufficient neural crest cell migration. This could explain the tachycardia and other functional cardiac pacing abnormalities observed in FAS infants. The population densities of cardiac intrinsic parasympathetic ganglion cells in ethanol- exposed and control rats will be assessed pre- and post-natally by histochemical and immunohistochemical techniques. It is also hypothesized that alcohol-induced redution in protein sysnthesis may inhibit the synthesis of Atrial Natriuretic peptide (ANP) in fetal atria and ventricles. ANP is a cardiovascular hormone with potent antihypertensive and vasoregulatory properties as well as antimitotic functions. Therefore, alteration in ANP content may affect cardiac development. Cardiac ANP content willb e monitored pre- and post- natally in ethanol-exposed and control

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rats by immunohistochemistry and radioimmunoassay. The results of the proposed studies should contribute significantly to understanding of the etiology of cardiac functional deficits related to FAS and lead to future studies at the molecular and cell biological levels of cardiac structural and functional abnormalities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ELECTRICAL THERAPY FOR PULSELESS ELECTRICAL ACTIVITY Principal Investigator & Institution: Ideker, Raymond E.; Jeanne V. Marks Professor; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2003 Summary: A serious problem during resuscitation to treat sudden cardiac arrest is that, even though defibrillation restores organized cardiac electrical activity, cardiac function is so poor that little or no blood is pumped, a condition called pulseless electrical activity (PEA). One is burst stimulation to restore a pulse pressure during PEA. The other is DC stimulation to improve function during chronic heart failure, which may also be beneficial during PEA. The other is DC stimulation to improve function during chronic heart failure, which may also be beneficial during PEA. In addition to their beneficial effects, these electrical stimuli may also have detrimental effects, the most serious of which is reinitiation of an arrhythmia. The goal of this project is to determine the mechanism of the beneficial and detrimental effects of burst and DC stimulation Electrical and optimal mapping will be used in animals to accomplish three specific aims. Specific Aim 1: To determine the effect of burst and DC stimulation on cardiac nerve activity. The hypothesis will be tested that the primary mechanism by which burst stimulation improves cardiac function is by increasing sympathetic nerve discharge. Specific Aim 2: To determine the effect of burst and DC stimulation on membrane polarization (Vm), action potential (APD), intracellular calcium (Cai/2+), and myocyte motion. The hypothesis will be tested that the primary mechanism by which DC stimulation improves cardiac function is by depolarizing Vm during the AP plateau, thus prolonging APD and increasing Cai2+. Specific Aim 3: To determine the mechanisms of the detrimental effects of burst and DC stimulation. The hypotheses will be tested that the mechanism for tachyarrhythmia induction by burst and DC stimulation are electroporation and creation of a Vm critical point. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ELECTRODE DESIGN FOR CARDIAC TACHYARRYTHMIA RF ABLATION Principal Investigator & Institution: Webster, John G.; Professor; Biomedical Engineering; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 01-SEP-1996; Project End 31-AUG-2004 Summary: (Adapted from Applicant's Abstract): The goal of this study is to optimize catheter design for the cure of atrial fibrillation and ventricular tachycardia by endocardial radiofrequency (RF) ablation. It is estimated that currently in the USA about 2 million people are affected by some form of atrial fibrillation. Also, each year about 200,000 patients are treated for ventricular tachycardia. Atrial fibrillation, although itself not fatal, is a frequent cause of stroke and is linked to a high degree of cardiovascular mortality. Ventricular tachycardia is the main cause of sudden cardiac death, affecting particularly patients suffering from myocardial infarction. To cure cardiac dysrhythmias, radiofrequency current flows through an electrode on a catheter in contact with the endocardium to ablate undesired arrhythmia substrates. This research

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will improve the electrodes and improve the procedure. In vitro tests on myocardium will yield physical parameters of electric conductivity, and thermal conduction, capacity, and heat convection variation throughout the endocardium. In vivo swine tests will improve accuracy of most parameters. The parameters will be used to improve a 3dimensional finite element computer model that simulates the electric power deposited, the myocardial temperature rise and the volume and distribution of the 50 degree Celsius contour that defines the lesion boundary. Further in vitro and in vivo tests will confirm the accuracy of the model. The model will predict lesion volumes resulting from proposed new electrodes. These are (1) uniform current density electrodes that prevent hot spots, steam generation "popping" and coagulum formation; (2) noncontact electrodes that generate larger lesions; (3) needle electrodes that generate larger lesions; (4) long electrodes that generate linear lesions for curing atrial fibrillation; (5) balloon electrodes that permit large imprints; (6) cooled electrodes; and (7) other novel electrodes. The model will aid in the design of new electrodes. The model will also predict the lesion volume at each ablation site. These volume predictions will form guidelines for setting tip temperature to achieve desired lesion volume at each ablation site and thus enhance present ablation techniques. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENDOTOXIN ASSAY FOR ANALYSIS OF SEPTICEMIA DAMAGE Principal Investigator & Institution: Segal, Gershon; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002 Summary: In the United States, septicemia is the 13th leading cause of death, and accounts for $5 - 10 billion health care dollars spent annually. Patients at risk of developing sepsis frequently present initially to the Emergency Department (ED), with a 'preseptic' syndrome, known as 'systemic inflammatory response syndrome' (SIRS). Prompt recognition, evaluation and initiation of therapy in this group of patients is an area of intensive investigation, since early therapeutic intervention with well established modalities (intravenous fluids and antibiotics) has been shown to be associated with improved outcomes. Furthermore, advances in understanding of the pathophysiology of bacteremia has opened the door for the development of additional therapeutics (e.g. antiendotoxin antibodies) for interrupting the cascade of events associated with full blown sepsis. Establishing an early diagnosis of septicemia remains challenging however. Not all patients with SIRS (fever, tachycardia, tachypnea, and elevated white blood cell count) have a bacterial infection. SIRS can also occur in patients with severe trauma, pancreatitis, and burns without infections. Additionally, demonstration that an infection is the inciting stimulus for SIRS is complicated by the fact that culture reports are usually not available for 24-48 hours, and blood cultures are positive in only about 60% of cases of sepsis. A sensitive and specific clinical diagnostic test for earlier detection of infection would allow physicians to make the diagnosis of septicemia more rapidly, and identify patients who would benefit from specific therapy. Previous efforts toward the development of an assay for early detection of bacteremia have focused on gram-negative infections, as these bacteria are responsible for the majority of cases of sepsis in the United States. The only test currently available assay, the Limulus amebocte lysate test (LAL) is an indirect semiquantitative assay, which has variable sensitivity and specificity and is thus utilized only for industry and research purposes. Recent investigations from the sponsor of this protocol (LINK technology) have demonstrated that a ligand binding assay (LBA) exceeds the sensitivity and specificity of the LAL for the detection of endotoxin in plasma, and may therefore provide the first

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clinically useful test for early identification of patients with gram negative septicemia. LINK's endotoxin test is based on the core discovery that endotoxin binds to an A1 adenosine receptor. A sensitive and specific clinical diagnostic that quantitates the level of endotoxin in blood has a broad range of clinical uses including: (a) early diagnosis of gram negative septicemia allowing for antibiotic specific therapy; (b) early prediction of impending organ dysfunction; and (c) monitoring of the effectiveness of antibiotics or other therapeutic agents targeted at eradicating the infection and treating the complications associated with gram negative bacteremia. We hypothesize that the detection of endotoxin in human blood by a LBA is an early, sensitive, and specific predictor of organ dysfunction associated with gram negative septicemia. The following specific objectives for this pilot study are: 1) to establish the relationship between the LBA and organ dysfunction; 2) to estimate the correlation of diagnostic errors between the LBA and blood culture; and 3) to identify potential confounders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FACTORS THAT INITIATE ARRHYTHAMIAS IN LONG QT SYNDROME Principal Investigator & Institution: Salama, Guy; Professor; Cell Biology and Physiology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2003; Project Start 01-FEB-1998; Project End 31-MAR-2007 Summary: (provided by applicant): The role of the autonomic nervous system in the genesis of life-threatening arrhythmias has been the subject of intense investigation yet remains incomplete and fragmented. Sympathetic imbalance has been implicated as a trigger of ventricular arrhythmias in the long QT syndrome (LQTS) by enhancing spatial heterogeneities of i) action potential durations (APDs), ii) dispersion of repolarization (DOR) and iii) perhaps conduction. The project will address fundamental questions regarding the neuromodulation of cardiac function by autonomic activity, the effects of intra-cardiac reflex responses and their role in LQT-related arrhythmias. Rabbit hearts will be isolated with bilateral innervation of sympathetic and parasympathetic branches, will be perfused, stained with voltage and Ca 2+ - sensitive dyes to simultaneously map action potentials (APs) and intracellular Ca 2v(Cai) transients from 256 sites at high spatial and temporal resolution. The sympathetic system will be stimulated bilaterally with electrodes inserted in the vertebral column and the parasympathetic system with electrodes on the right and left vagus nerves. Innervated hearts will be perfused with inhibitors of IKs (HMR 1556), IKr (E4031) or INa inactivation kinetics (Anthopleurin A) (e.g. models of LQTS types 1-3) to elucidate the role of autonomic activity on Torsade de Pointes (TdP). The specific aims are: 1) To test the hypothesis that autonomic activity to the heart modulates APDs, DOR and to determine the mechanisms underlying this neuromodulation by mapping simultaneously cardiac APs and Cai from 256 sites of innervated, Langendorff rabbit hearts. Sympathetic and parasympathetic modulation of heart rate, conduction of the specialized conduction system and ventricular myocardium, AP upstroke velocity, APDs, DOR, and Cai transients will be analyzed during various autonomic nerve stimulation paradigms. Stimulation nerve paradigms will be developed to obtain a spectrum of cardiac responses. Pharmacological interventions will be used to identify the receptors mediating the cardiac responses (131,132,cq-adrenergic receptors: AR; muscarinic cholinergic; peptidergic and puronergic) and the contribution of efferent and afferent fibers involved in this neuromodulation by blocking ganglionic transmission with hexamethonium. 2) To test the hypothesis that intra-cardiac reflexes via afferent and efferent neurons and ganglia

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in the heart muscle regulate electrical and contractile properties. We will apply a focal sensory stimulus (mechanical or chemical) at a site on the heart (i.e. the apex of the left ventricle) while recording changes in electrical and contractile parameters mediated by cardiac reflex responses in other regions of the heart. Pharmacological agents will then be per'fused to block specific neural pathways to identify the underlying neuronal mechanisms. 3) The synergistic effects of right and left sympathetic or right-left vagus nerves activation and the cross-interactions between the sympathetic and parasympathetic branches are central to our understanding of the neuromodulation of the heart. We will compare the changes in APs and Ca_ at a constant heart rate during i) bilateral versus unilateral (right or left) vagal stimulation; ii) vertebral column stimulation (bilateral sympathetic activation) and bilateral versus unilateral vagus stimulation; iii) vertebral column stimulation with right or left stellectomy. Sympathetic inputs to the heart are fractionated and emanate from different thoracic segments that target different regions of the heart. We will selectively stimulate a single sympathetic branch without activating the others inputs (up to 4) to identify the targets on the heart of each input. The convergence or divergence of sympathetic inputs to the heart may be important for normal cardiac function and enhance QT dispersion and TdP in the LQTS. 4) The role of 'autonomic imbalance' on the genesis of LQT-related arrhythmias will be determined in rabbit heart with LQTS type 1,2 or 3 by measuring changes in APDs, DOR, the propensity to fire early afterdepolarizations (EADs) and the initiation of TdP before and during various nerve stimulation paradigms (determined in aim 1). Stimulation paradigms that i) enhance DOR or ii) elicit a bradycardia followed by a tachycardia are more likely to increase the incidence of EADs and TdP. The specific aims are: 1) To test the hypothesis that autonomic activity to the heart modulates APDs, DOR and to determine the mechanisms underlying this neuromodulation by mapping simultaneously cardiac APs and CaI from 256 sites of innervated, Langendorff rabbit hearts. Sympathetic and parasympathetic modulation of heart rate, conduction of the specialized conduction system and ventricular myocardium, AP upstroke velocity, APDs, DOR, and CaI transients will be analyzed during various autonomic nerve stimulation paradigms. Stimulation nerve paradigms will be developed to obtain a spectrum of cardiac responses. Pharmacological interventions will be used to identify the receptors mediating the cardiac responses (beta1, beta2, alpha1-adrenergic receptors: AR; muscarinic cholinergic; peptidergic and puronergic) and the contribution of efferent and afferent fibers involved in this neuromodulation by blocking ganglionic transmission with hexamethonium. 2) To test the hypothesis that intra-cardiac reflexes via afferent and efferent neurons and ganglia in the heart muscle regulate electrical and contractile properties. We will apply a focal sensory stimulus (mechanical or chemical) at a site on the heart (i.e. the apex of the left ventricle) while recording changes in electrical and contractile parameters mediated by cardiac reflex responses in other regions of the heart. Pharmacological agents will then be perfused to block specific neural pathways to identify the underlying neuronal mechanisms. 3) The synergistic effects of right and left sympathetic or right-left vagus nerves activation and the crossinteractions between the sympathetic and parasympathetic branches are central to our understanding of the neuromodulation of the heart. We will compare the changes in APs and Cai at a constant heart rate during i) bilateral versus unilateral vagus stimulation; ii) vertebral column stimulation (bilateral sympathetic activation) and bilateral versus unilateral vagus stimulation; iii) vertebral column stimulation with right or left stellectomy. Sympathetic inputs to the heart are fractionated and emanate from different thoracic segments that target different regions of the heart. We will selectively stimulate a single sympathetic branch without activating the others inputs (up to 4) to identify the targets on the heart of each input. The convergence or divergence of sympathetic inputs to the heart may be important for normal cardiac function and

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enhance QT dispersion and TdP in the LQTS. 4) The role of 'autonomic imbalance' on the genesis of LQT-related arrhythmias will be determined in rabbit heart with LQTS type 1, 2, or 3 by measuring changes in APDs, DOR, the propensity to fire early afterdepolarizations (EADs) and the initiation of TdP before and during various nerve stimulation paradigms (determined in aim 1). Stimulation paradigms that i) enhance DOR or ii) elicit a bradycardia followed by a tachycardia are more likely to increase the incidence of EADs or TdP. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENDER & ORTHOSTATIC INTOLERANCE: MECHANISMS AND THERAPY Principal Investigator & Institution: Fu, Qi; Internal Medicine; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2004; Project Start 15-APR-2004; Project End 31-MAR-2009 Summary: (provided by applicant): The global objective of this Mentored PatientOriented Research Career Development Award is to build my career as an academic physician-scientist and make the transition to become an independent investigator. To accomplish this goal, together with my mentor, i have developed a tightly integrated plan including cutting edge science, and advanced training in the techniques of patientoriented research. By participating in the K30 Curriculum in Patient-Oriented Research at UT Southwestern leading towards a MPH degree, I will receive in-depth instruction in research design, protection of human subjects, grantsmanship, and advanced level biostatistics. From my mentor and advisory committee, made up of senior scientists both at UT Southwestern and at the Brigham and Women's Hospital, I also will acquire critical new research skills regarding renal/neurohormonal mechanisms of blood pressure control, reproductive endocrinology, and clinical orthostatic intolerance. My research plan focuses on the mechanisms underlying gender differences in orthostatic tolerance, including neurohumoral influences on cardiovascular control processes and physical characteristics (primarily cardiac size and function) that determine orthostatic distribution of central blood volume. Menstrual cycle variability in young women, and differences among men, women, and women with chronic orthostatic intolerance (Postural Orthostatic Tachycardia Syndrome, or "POTS") will be examined. Finally, a specific intervention (exercise training) will be studied as treatment for patients with POTS and compared with standard pharmacologic therapies (13-blockers and volume expanders). Autonomic neural control of hemodynamic and sympathetic responses to the Valsalva maneuver, static handgrip, a cold pressor test, and prolonged head-up tilt will be investigated; the venoarteriolar response and neurohumoral responses to a longterm standing will be examined. After completion of the proposed project, we will know whether gender-specific factors such as the menstrual cycle or physical factors influencing cardiac size and function are among the determinants for orthostatic intolerance in young women, and whether physical exercise training can be considered an effective non-pharmacologic treatment for patients to improve their orthostatic tolerance. The combination of advanced training in patient-oriented research and indepth study of an important clinical problem will prepare me well for a career as an independent investigator. (End of Abstract) Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENE DISCOVERY IN A PUTATIVE MOUSE MODEL OF ADHD Principal Investigator & Institution: Mcdonald, Michael P.; Assistant Professor; Pharmacology; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917

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Timing: Fiscal Year 2003; Project Start 15-JAN-2003; Project End 31-DEC-2004 Summary: (provided by applicant): Abnormal thyroid levels during gestation can have devastating effects on brain development and cognition. Resistance to thyroid (RTH) syndrome is a heritable condition caused by mutations in the TRbeta gene that typically result in elevated thyroid hormones, short stature, and tachycardia. More than half of RTH patients have attention deficit hyperactivity disorder (ADHD), with the incidence about 50% higher among males. Although the etiology of ADHD is unknown, considerable evidence implicates deficiencies in the dopaminergic and noradrenergic neurotransmitter systems. A normally functioning thyroid system is critical for proper development of the catecholaminergic systems, and thyroid abnormalities can result in behavioral and neurochemical features consistent with ADHD. We have recently found that a TRbeta transgenic mouse bearing a human mutant thyroid beta1 receptor reproduces all of the key symptoms of ADHD, such as juvenile hyperactivity, deficits in sustained and selective attention, impulsivity, and reduced catecholamine levels. Interestingly, the TRbeta transgenic mice have normal levels of thyroid hormones, thyroid stimulating hormone (TSH), and suppression of TSH. This is intriguing because it raises the possibility that modest developmental thyroid dysfunction may contribute to a larger proportion of ADHD cases than previously thought. In addition to the core symptoms of the disorder, mice demonstrate many of the more subtle features of ADHD, e.g., the hyperactivity dissipates in adulthood, the penetrance is greater among males than among females, and the deficit in sustained attention is attenuated with greater reinforcement levels. Another interesting feature of the TRbeta transgenic mice is that the hyperactivity phenotype depends on the maternal genotype, independent of the mouse's own genotype. This suggests a possible biological or behavioral basis for maternal or environmental effects on ADHD subtypes. This high degree of analogy between complex human behavioral disorders in an animal model is unparalleled for a complex, multigenic behavioral disorder. We propose to use microarray technology to examine differential gene expression in wild-types vs. transgenics, males vs. females, and offspring of transgenic dams vs. offspring of wild-type dams, in pups, adolescents, and adults. The TRbeta transgenic mouse model provides us with a rare opportunity to discover genes downstream of TRbeta activity that are able to produce all of the core symptoms and many adjunct features of ADHD-genes that may be differentially expressed in a large number of children with ADHD. In addition, we have an unprecedented opportunity to discover how the relationship between gene expression and behavior differs according to diagnostic subtype, gender, treatment refractoriness, and environmental (e.g., maternal) conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC AND RECEPTOR MECHANISMS IN HYPERTENSION Principal Investigator & Institution: Printz, Morton P.; Professor; Pharmacology; University of California San Diego La Jolla, Ca 920930934 Timing: Fiscal Year 2003; Project Start 01-MAR-1986; Project End 30-APR-2008 Summary: (provided by applicant): Research efforts of this Program Project are designed to identify and map genes in newly discovered quantitative trait loci (QTL) and to elucidate their contributions to susceptibility to genetic hypertension and target organ damage. Four projects supported by five cores comprise this Program. The Program theme emphasizes genomics of the effect of stressors on aberrant cardiovascular responses in the SHR, unique genetic rodent models, including the only colony of HXB-BXH rat Recombinant Inbred (RI) strains outside of Europe, and the pursuit of genes which (a) determine resting arterial pressure, (b) determine autonomic

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responses to environmental and behavioral stress, or (c) determine susceptibility to hypertension from repeated episodes of stress. The first subproject will seek candidate genes in new QTL discovered for mild airpuff startle stress-elicited tachycardia and pressor responses, for bradycardia associated with the Orienting Response, and for a cluster of blood pressure QTL on chromosome 2. Dr. Kurtz's subproject will build on its studies of the genes, Srebp-1 and CD36, and their role in abnormal lipid, glucose and plasma insulin in the SHR. Dr. Nigam's subproject will study the cell biology and mechanisms of action of new and unknown factors which exert inhibition on the formation of the developing ureteric tree and ultimately nephron number. Dr. Taylor's subproject will continue studies of hyper-responsiveness of spinal nicotinic receptors in the SHR and define the gene structure of nicotinic receptor subunit genes, which are in close proximity to a blood pressure locus. Cores will provide the folkowing functions: administration; breeding of rodents; telemetry and phenotyping, statistical genetic analyses, gene discovery, informatics and genotyping. The contributions of this Program should enhance our knowledge of genes, which determine susceptibility to repeated stress, to hypertension, to metabolic risk factors and to target organ damage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC DETERMINANTS OF SUDDEN CARDIAC DEATH Principal Investigator & Institution: Albert, Christine M.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 05-JUL-2003; Project End 30-JUN-2007 Summary: (provided by applicant): Sudden cardiac death (SCD) affects 400,000 individuals each year in the U.S. alone. Over half have no evidence of heart disease prior to death, and our ability to identify those at risk and therefore prevent SCD is poor. Mutations in cardiac ion channel genes including SCN5A, KVLQT1, HERG, KCNE1, KCNE2, and RyR2 have been implicated in monogenic traits with a high risk of SCD, such as the Iong-QT, Brugada, sudden infant death syndrome, and catecholaminergic polymorphic ventricular tachycardia. Alterations in ion channel function can result in life-threatening ventricular arrhythmias in diverse disease states. Therefore, sequence variants in these genes that alter function or transcription of these ion channels may confer a predisposition to ventricular arrhythmia and SCD in broader populations. This research program proposes to determine if sequence variants in the above candidate genes are associated with an increased risk of SCD in apparently healthy populations. Cases of SCD will be assembled from five NIH-funded prospective cohorts with a total of 106,314 individuals with existent blood samples. All cohorts are exceptionally wellcharacterized with respect to environmental exposures and have collected medical records on cardiovascular endpoints. We will characterize all coding sequence variation and selected non-coding sequence variation among 100 cases and controls from these cohorts. Using these novel markers, we will define the haplotype block structure (SNPs in linkage disequilibrium) for the six genes. We will then employ a nested case-control design and conditional logistic regression to test for associations between haplotypes (haplotype tag SNPs) in both coding and non-coding regions and SCD risk. We will also test directly for associations between single loci that may have functional significance and SCD risk. An estimated 600 cases of well-documented SCD will be confirmed over the first three years of the grant period, and these cases will be matched on age, sex, ethnicity, and geographic location to two control subjects from the same cohort. In addition, based upon known sex-differences in the phenotypic expression of the candidate genes in the primary arrhythmic disorders, we will specifically examine sexdifferences in the risk of SCD associated with sequence variation in these genes. The

34

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findings generated will have substantial implications for our understanding of the SCD syndrome and risk stratification in the general population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC SUSCEPTIBILITY IN ACQUIRED LONG QT SYNDROME Principal Investigator & Institution: Murray, Katherine T.; Associate Professor; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-DEC-2001; Project End 30-NOV-2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GUIDANT & CPI VENTAK FOR CONGESTIVE HEART FAILURE Principal Investigator & Institution: Birgersdotter, Ulrika; University of California San Diego La Jolla, Ca 920930934 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HYPOTHERMIA FOR PEDIATRIC CARDIAC ARREST PLANNING GRANT Principal Investigator & Institution: Moler, Frank W.; Pediatrics & Communicable Dis; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2003; Project Start 24-JUL-2003; Project End 30-JUN-2005 Summary: (provided by the applicant): Cardiopulmonary arrest with apnea and loss of palpable pulse (CA) in childhood is a tragic event that very often results in either death or poor quality long-term neurological survival. Recent randomized clinical trials (RCT) in adult populations have reported improved neurologic outcome and survival in groups that received short term mild hypothermia following out of hospital ventricular fibrillation (VF) arrest. The efficacy of hypothermia in children following cardiac arrest is not known. CA in children is commonly secondary to a respiratory etiology that results in hypoxia, which after a period of time results in cardiac arrest. Asystole or pulseless electrical activity are the most common presenting cardiac rhythms when resuscitation is initiated. In adults by contrast, a sudden cardiac event (without a preceding period of hypoxia) most often occurs with VF or ventricular tachycardia, the common presenting rhythms. In this clinical trial planning grant application, 15 Pediatric Emergency Care Applied Research Network (PECARN) children's hospitals with intensive care units will obtain pilot data from the medical records of patients who have sustained a CA with return of spontaneous circulation in either the outpatient or inpatient setting. Characterization of this population will include arrest specific events and etiology, patient characteristics, hospital course, interventions received, hospital survival, and neurologic outcome. This information will be used to create inclusion and exclusion criteria, and to calculate sample size requirements for a future RCT of hypothermia following pediatric cardiac arrest. Duration of time to successfully enroll patients from this cohort of 15 children's hospitals for a future RCT will be estimated. This application will also result in creation of multiple documents needed to perform a RCT of hypothermia after cardiac arrest in childhood including study related data forms, study protocols, manuals of operation, institutional review board and informed

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consent related documents, and other materials. The PECARN will support all phases of this application with its existing clinical trials research infrastructure that includes a steering committee, five clinical trials supporting subcommittees, and a central data management coordinating center (CDMCC). The CDMCC will make operational all data and analysis related tasks of this application, and assure all study sites are compliant with regulations concerning data security and confidentiality. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LASER TACHYCARDIA

CATHER

FOR

ABLATION

OF

VENTRICULAR

Principal Investigator & Institution: Gowda, Ashok; Biotex, Inc. 8018 El Rio Houston, Tx 770544104 Timing: Fiscal Year 2002; Project Start 28-SEP-1999; Project End 31-JUL-2004 Summary: (provided by applicant): Ventricular Tachycardia (VT) is a life-threatening condition characterized by an abnormally high rate of ventricular contraction. During VT, the ventricles lack sufficient time to fill with blood prior to each contraction often resulting in dizziness, loss of consciousness and sudden cardiac arrest. Catheter ablation has been shown to be an effective means for curing many arrhythmias, but current approaches are not able to coagulate tissue in the midmyocardium or subepicardial regions where foci responsible for VT often originate. We have developed a cooled-tip laser catheter (CTLC) capable of creating large lesions that extend into these regions with little to no thermal damage to the endocardium. In our phase I study we designed, built, and tested prototypes of the CTLC system. The current system is comprised of an 8F deflectable catheter, which houses a fiber optic and a pathway for circulation of saline. We incorporated a low cost pump system and a low-power diode laser to complete the system. Acute and chronic animal studies were performed to test the prototype system and the results were indeed dramatic. Using our CTLC system, we successfully produced large (1 cm in diameter) lesions that began on average 1 mm below the irradiated surface. These lesions were free of char or carbonization and well circumscribed by a distinct border separating the lesion form normal tissue. Additional advantages of our approach include the ability to monitor real-time electrophysiological activity during delivery of laser energy. In Phase II we plan to refine the current CTLC by including functional mapping electrodes and improving maneuverability. Animal studies are designed to characterize in a thorough manner the dose response for our system, compare it against current state of the art ablation technologies, and acquire data necessary for submission of an investigational device exemption from the FDA for clinical trials. PROPOSED COMMERCIAL APPLICATION: This research is specifically targeted towards the development of an improved laser-based catheter for treatment of VT. Cardiac arrhythmias including ventricular tachycardia (VT) and ventricular fibrillation (VF) are responsible for 400,000 cases of sudden death in the U.S. each year. Unlike other therapies, our catheter has potential for providing a curative means for patients who suffer from VT, and therefore could become the treatment of choice in such patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LIGAND BINDING AND FUNCTIONAL ASSAY-BASED HERG DATABASE Principal Investigator & Institution: Perschke, Scott E.; Novascreen Biosciences Corporation 7170 Standard Dr Hanover, Md 21076

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Timing: Fiscal Year 2002; Project Start 25-SEP-2002; Project End 24-MAR-2003 Summary: (provided by applicant): The HERG (human ether-a-go-go-related) gene encodes a membrane protein that functions as a K+ -channel. There is intense interest in the HERG protein because interactions between drugs and the HERG channel protein have become a major impediment in the development of new and safe pharmaceuticals. Interactions of drugs with the HERG channel alter the repolarization of the hearts' electrical system, causing tachycardia and occasionally heart failure. This has led to the removal of at least one drug from the market, and caused many others to fail in clinical trials. There is an increasing demand for methodologies that will allow prediction and identification of lead compounds with potential HERG channel activity early in the drug discovery process. The specific aims of this proposal are to develop multiple ligand binding assays and a functional assay for the HERG channel, as expressed in CHO cells. Once developed, approximately 20 known HERG inhibiting drugs will be screened for dose response in all assays developed and the data collected and assembled in a database. This database will then be used as the basis for a Phase 2 study that greatly expands the chemicals tested, to identify key molecular and chemical descriptors that are predictive of drug and protein interactions with the channel. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISM TACHYCARDIA

AND

BEHAVIOR

OF

SYMPTOMATIC

Principal Investigator & Institution: Pritchett, Edward L.; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISM OF ARRHYTHMIAS IN THE SETTING OF HEART FAILURE Principal Investigator & Institution: Pogwizd, Steven M.; Associate Professor; Medicine; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 09-AUG-1991; Project End 31-JUL-2003 Summary: The goal of the proposed studies is to define the electrophysiologic and subcellular mechanisms underlying nonreentrant initation of ventricular tachycardia (VT) in the failing heart and its modulation by adrenergic stimulation. In the preceding grant interval, we have performed 3- dimensional mapping studies in arrhythmogenic experimental models of cardiomyopathy and in the failing human heart and demonstrated that VT initiates by a nonreentrant mechanism that is enhanced by catecholamines. The applicant has isolated myocytes from failing hearts and found alterations in Na/Ca exchange activity and intracellular calcium handling that could underlie the development of an arrhythmogenic transient inward current (Iti). Studies will be performed both in an arrhythmogenic rabbit model of nonischemic cardiomyopathy and in the failing human heart. The contribution of Alpha1-, Beta1- and Beta2-adrenergic receptor stimulation to arrhythmogenesis in the failing heart will be determined by in vivo 3-dimensional mapping and in vitro electrophysiologic studies. Measurement of Alpha1-, Beta1-, and Beta2- adrenergic receptor density with microscopic resolution using autoradiographic techniques will determine whether the density of adrenergic subtype receptors parallel the arrhythmogenic effects of adrenergic subtype stimulation. To delineate how alterations in sarcoplasmic reticulum

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(SR) calcium flux, Na/Ca exchange activity and a calcium-activated chloride current lead to activation of a Iti in the failing heart, and to determine how the activation of Iti is enhanced by adrenergic stimulation, whole cell voltage clamping and measurement of intracellular calcium and SR calcium content will be performed in myocytes isolated from myopathic hearts. Lastly, to determine whether nonreentrant activation is due to triggered activity arising from delayed afterdepolarizations (as opposed to early afterdepolarizations or abnormal automaticity), studies will be performed in a novel isolated heart preparation in which transmural mapping in vitro will be combined with recording of monophasic and transmembrane action potentials. The results of these studies will provide new insights into the nature of nonreentrant activation in the failing heart and of the subcellular alterations that underlie adrenergic enhancement of arrhythmogenesis. The results will also provide the foundation for novel therapeutic approaches directed at nonreentrant activation that would be useful in the prevention of sudden death in patients with cardiomyopathy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF DEPRESSION AND CARDIOVASCULAR PATHOLOGY Principal Investigator & Institution: Grippo, Angela J.; Psychology; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 01-APR-2002 Summary: (provided by applicant): This research proposal addresses physiological mechanisms and processes underlying the association between depression and cardiovascular disease. Human studies demonstrate a strong link between depression and coronary artery disease but have not progressed beyond correlational methods. The current proposal will examine the underlying mechanisms in depression and cardiovascular pathology by using a rodent model of depression (chronic mild stress) and a combination of behavioral, physiological, and pharmacological techniques. Rats will be exposed to chronic mild stress to induce the depression-associated sign of anhedonia (a reduced capacity to experience pleasure), and tested for cardiovascular impairments (Aim 1). Autonomic nervous system imbalance will be examined as a mechanism for the cardiovascular dysfunction (e.g., elevated heart rate and reduced heart rate variability) associated with the chronic mild stress model (Aim 2). In addition, central serotonin activity will be examined as a common pathophysiological factor underlying both depression and cardiovascular/autonomic dysfunction (Aim 3). This research will extend our knowledge of the interactions between psychological and physiological conditions, and possibly prompt the development of new treatments for patients with depression and/or cardiovascular disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISMS OF SYMPTOMS IN NEUROPATHIC PAIN & RSD Principal Investigator & Institution: Dotson, Rose; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002 Summary: The hypothesis and specific aims are focused on the pathophysiology of two different groups of conditions. The first group is orthostatic intolerance, specifically the postural tachycardia syndrome (POTS). The second group is neuropathic pain. The studies on neuropathic pain have been organized into 2 types of painfulness in response to a normally non-painful stimulus (allodynia) and to the enigma of reflex

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symmpathetic dystrophy. The allodynias are in response to light touch (dynamic allodynia) and to pressure (static allodynia). The primary hypothesis is that patients with POTS develop a post-viral, presumably immune-mediated length-dependent autonomic neuropathy and that secondary brain-stem mechanisms supervene, resulting in a hyperadrenergic state. We will evaluate the pathophysiology of orthostatic intolerance using microneurographic recordings of muscle sympathetic nerve activity from peroneal nerves of patients with the postural tachycardia syndrome (POTS) and controls. We will specifically evaluate if resting muscle sympathetic nerve activity is increased (due t increased central drive) or reduced (due to denervation) and, to evaluate varoflex responsiveness, if the response to orthostatic stress and to induced blood pressure alterations are impaired. The hypothesis for the study of patients with neuropathic pain who have dynamic mechanical allodynia is that low threshold mechanoreceptor primary afferents propagate neural impulses to the central nervous system and result in the experience of pain with dynamic mechanical allodynia. The study will determine if rapid repetitive intraneural microstimulation of single low threshold mechanoreceptor primary afferents in patients with peripheral neurogenic pain and dynamic mechanical allodynia causes pain as the first perceived sensation with liminal intensity (the lowest intensity at which the subjects reports a perceived sensation) of electrical stimulation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANO-ELECTRIC FEEDBACK IN THE HEART Principal Investigator & Institution: Trayanova, Natalia A.; Professor; Tulane University of Louisiana New Orleans, La New Orleans, La 70112 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2006 Summary: SUBPROJECT ABSTRACT NOT PROVIDED Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MODE SELECTION TRIAL IN SINUS NODE DYSFUNCTION (MOST) Principal Investigator Washington, Dc 20059

&

Institution:

Williams,

Deborah;

Howard

University

Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MODULATION OF CARDIAC K+ CHANNELS BY DRUGS Principal Investigator & Institution: Sanguinetti, Michael C.; Associate Professor; Internal Medicine; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2002; Project Start 01-JUL-1996; Project End 30-JUN-2005 Summary: Drugs that block the rapid delayed rectifier K+ current (Ikr) cause prolongation of cardiac action potentials and electrical refractoriness. These compounds were developed as antiarrhythmic agents based on positive findings in canine models of ischemia-induced ventricular tachycardia and fibrillation. Unfortunately, most class III antiarrhythmic drugs, as well as 70 other common mediations that block Ikr as a sideeffect, can cause an inhomogeneous prolongation of ventricular action potentials and induce long QT syndrome and its associated ventricular arrhythmia, torsades de pointes. It is unclear why so many structurally diverse compounds block Ikr, but this

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undesirable side effect is now recognized as a major hurdle in the development of new and safe drugs. The recent awareness that block of Ikr can induce arrhythmias prompted interest in the development of IKs blockers as antiarrhythmic agents. However, in the past 5 years it was discovered that mutations in any of the genes that encode the alpha- and beta-subunits that co assemble to form Ikr (HERG and MiRPl or IKs (KvLQT1 and minK) channels cause inherited long QT syndrome and sudden death. The overall goal of this project arises from our progress during the past four years where we defined the mechanisms of Ikr block and the molecular determinants of binding of a potent class III antiarrhythmic agent to the HERG channel. We now propose to characterize the blocking mechanisms and binding site for additional antiarrhythmic agents and other commonly used medications that block Kr and Ks channels. The specific aims are to characterize the molecular determinants of high affinity drug block of HERG and KvLQT1 channels, the role of the inactivated state in drug block of HERG channels, and how binding of accessory beta-subunits (minK, MiRP1 and MiRP2) enhances drug block of HERG and KvLQT1 channels. An understanding of the molecular determinants of drug binding to Kr and Ks channels will facilitate design of safer drugs that are devoid of the propensity to induce the long QT syndrome and potentially fatal arrhythmias. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR MECHANISMS OF CARDIAC ARRHYTHMIAS Principal Investigator & Institution: Wang, Qing; Cleveland Clinic Foundation 9500 Euclid Ave Cleveland, Oh 44195 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 30-JUN-2006 Summary: (provided by applicant): Cardiac arrhythmias account for more than 300,000 sudden deaths each year in the U.S. alone. Our laboratory is investigating the pathogenesis of cardiac arrhythmias. We focus on two arrhythmic disorders: long-QT syndrome (LQT) and idiopathic ventricular fibrillation (IVF), both of which cause sudden death in the young, otherwise healthy, individuals. During the past 8 years of this project, we focused on genetics and in vitro electrophysiology of LQT and IVF. Together with other scientists, we have defined a genetic pathway for pathogenesis of both LQT and IVF. Further exploration of pathogenic mechanisms of LQT and IVF at the tissue and organ level is impossible because of lack of fresh heart tissues from patients. In the proposed studies we plan to develop and characterize LQT- and IVF-animal models in which SCN5A (the cardiac sodium channel gene) mutations are engineered into the mouse genome to further explore the etiology of arrhythmogenesis. We have successfully established a mouse model for LQT and ventricular arrhythmias by targeting an SCN5A mutation (N1325S). Characterization of our arrhythmic mice has led to the working hypothesis that early and after depolarizations (EADs and DADs) are the substrate for ventricular tachycardia (VT) and ventricular fibrillation (VF). In the proposed studies we plan to continue to study the mouse model for LQT to uncover detailed molecular mechanisms of cardiac arrhythmias, and to generate and characterize mouse models for IVF and acquired LQT. Our specific aims are: (1) To investigate whether over-expression of an LQT-causing mutation of SCN5A in the mouse heart will trigger electrophysiological remodeling; (2) To systematically dissect EADs and DADs induced by a genetic LQT mutation; (3) To systematically determine the effects of representative agents from each class of antiarrhythmic drugs on VT/VF and correlate the findings with results on EADs/DADs; (4) To characterize SCN5A mutations associated with IVF and acquired LQT using the transgenic mouse technology. The successful accomplishment of goals in this proposal will provide a fundamental

40

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understanding of the pathogenic mechanisms of cardiac arrhythmias. Evaluation of animal models will help define the physiological and cellular processes involved in arrhythmogenesis, and bridge the gap between the in vitro biophysical defects and the in vivo whole animal phenotype characterized by arrhythmia susceptibility. These studies may provide a new framework for the rational design of therapeutic agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR STUDIES OF GAP JUNCTION REMODELING Principal Investigator & Institution: Fishman, Glenn I.; William Goldring Professor; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2002 Summary: Description (Adapted from Applicant's Abstract) Several lines of investigation suggest that dysregulation of gap junction intercellular communication, or gap junctional remodeling, contributes to the substrate for ventricular arrhythmias. Using the canine infarct model, investigations in this Program have shown that changes in the structural location of gap junctions and the electrophysiological properties of gap junctions are associated with functional lines of block in reentrant circuits. Similar gap junctional remodeling has also been observed in human ischemic cardiomyopathy and in our studies of genetically modified mice with ventricular tachycardia and sudden cardiac death. Myopathic hearts, however, show a multitude of structural and functional perturbations, thus, the unique arrhythmias has been difficult to study in isolation from other contributory factors. The goal of the studies described in this proposal is to understand the molecular mechanisms of gap junctional remodeling and to determine the specific contribution of dysregulated intercellular coupling to the formation of the arrhythmogenic substrate. The applicant has, therefore, begun to elucidate mechanisms controlling gap junctional expression and remodeling and discovered that the Wnt signaling cascade, acting through beta-catenin via duel transcriptional and post-translational mechanisms, is an important regulatory pathway controlling connexin43 expression. Furthermore, they have prepared several conditions gene-targeted murine models to elucidate the role of remodeling in formation of the arrhythmogenic substrate. Their goals in junctional remodeling, conduction abnormalities and arrhythmogenesis, using gene-targeted and chimeric mice; 2) to determine the role of beta-catenin mediated signaling and its relationship with other signaling pathways in the regulation of Cx43 expression in normal and remodeled cardiomyocytes and hearts; 3) to determine the mechanisms responsible for gap junctional reentrant excitation appears to be related to changes in gap junction distribution. Elucidation of the mechanisms regulating gap junctional remodeling and its role in the arrhythmogenic substrate have significant implications for novel pharmacotherapy of lethal cardiac arrhythmias. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR TARGETING OF CA2+ AND K+ CHANNELS IN HEART Principal Investigator & Institution: Kass, Robert S.; Professor of Pharmaclogy and Chairman; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2002 Summary: Description (Adapted from Applicant's Abstract) The overall goal of the research proposed in this project is to identify molecular properties of cardiac ion channel proteins and organic drug molecules that will allow targeted control of calcium

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entry in cardiac myocytes in general and in myocytes surviving in the border zone of infarcted hearts in particular. Motivation for this goal comes from data in other projects of this program where it was shown that increasing L-type calcium channel current may prevent reentrant tachycardia in the infarcted canine heart, and that functional and molecular properties of key ion channels (Na+, Ca2+, and K+) are altered in epicardial cells that survive in the epicardial border zone (EBZ) of infarcted hearts. The overall goal of this project is thus to provide molecular insight into mechanisms that would permit more precise targeting of drugs to control calcium entry in these cells. There are thus three specific aims of this project. (1) to identify molecular determinants that target potentiation of calcium entry to cardiac vs. smooth muscle L-type calcium channels: (2) to test the hypothesis that drug-induced changes in L-type Ca2+ channel deactivation kinetics is a powerful mechanism of modulating calcium entry into targeted cells; and (3) to test the hypothesis that subunit assembly of 1Ks channel, which may differ between normal and EBZ cells, confers unique pharmacological and regulatory properties upon expressed channels. Together this information will provide a molecular basis for targeting control of calcium entry into cells of the EBZ which, in combination with the data obtained from other Projects of this program will provide the framework for the development of novel anti-arrhythmic therapy to control reentrant arrhythmias in ischemia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MRI COMPATIBLE ELECTRODE CATHETER SYSTEM Principal Investigator & Institution: Gelfand, Yakov; Lexmed Technologies, Inc. 7708 Crossland Rd Baltimore, Md 21208 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2004 Summary: (provided by applicant): Atrial fibrillation and ventricular tachyarrhythmias occurring in patients with structurally abnormal hearts are the most important arrhythmias in contemporary cardiology. They represent the most frequently encountered tachycardias, account for the most morbidity and mortality, and, despite much progress, and remain therapeutic challenges. Invasive studies of the electrical activity of the heart (electrophysiologic study) are often used in the diagnosis and therapy of arrhythmias, and many arrhythmias can be cured by selective destruction of critical electrical pathways with radiofrequency (RF) catheter ablation. Attempts at applying ablation to atrial fibrillation and ventricular tachycardia have been made. Success has been limited, however, by the long time duration of procedures, resulting from the difficulty of creating continuous linear lesions in a setting where areas of ablated myocardium cannot be directly visualized. Continuous linear lesions, without gaps, can block critical arrhythmogenic circuits and reduce the amount of electrically contiguous arrhythmogenic substrate, thereby eliminating arrhythmias. We hypothesize that magnetic resonance imaging (MRI), with MRI-compatible diagnostic and therapeutic systems; can allow electrophysiology studies and catheter ablation to be performed without x-ray radiation. We also hypothesize that this technology will provide the ability to visualize ablation lesions, which should greatly simplify production of continuous linear lesions, and should improve the effectiveness of ablation procedures in general. In addition to electrophysiology, these methods may be applicable to guiding other diagnostic and therapeutic techniques. In Phase I, we will complete a prototype steerable ablation catheter that will allow us to target any area of the endocardial surface of the heart. We will also develop integral filters for protecting the catheters from excessive heating during MR imaging. We will test the prototype catheters in animals to show that electrophysiology studies can be done under MR

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guidance alone, that lesions can be produced and imaged, that linear lesions can be produced, and that MRI has sufficient resolution to allow detection of significant gaps in the lesions. In Phase II, we will develop, test, and prepare for manufacturing and marketing, a clinical-grade version of the ablation system, and apply for FDA approval for testing the technology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NERVE SPROUTING AND ELECTRICAL REMODELING Principal Investigator & Institution: Chen, Peng-Shen; Director, Pacemaker and Icd Clinic; Cedars-Sinai Medical Center Box 48750, 8700 Beverly Blvd Los Angeles, Ca 900481804 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-AUG-2004 Summary: The objective of this research project is to test the hypothesis that the interaction between neural remodeling (nerve sprouting) and electrical remodeling underlie the mechanisms of ventricular arrhythmogenesis after myocardial infarction (MI). We recently reported a positive correlation between the nerve density of native hearts of transplant recipients and a clinical history of ventricular arrhythmia. We also demonstrated in dogs that nerve growth factor (NGF) infusion to the left stellate ganglion could facilitate the development of ventricular tachycardia (VT), ventricular fibrillation (VF), and sudden cardiac death (SCD). Based on these findings, we propose Nerve Sprouting Hypothesis of ventricular arrhythmia and SCD. The hypothesis states that MI results in nerve injury followed by sympathetic nerve sprouting and regional myocardial hyperinnervation. The coupling between augmented sympathetic nerve sprouting with electrically remodeled ventricular myocardium results in VT, VF and SCD. Modification of nerve sprouting after MI may provide a novel opportunity for arrhythmia control. To test this hypothesis, we plan to pursue the following specific aims: (1) Mechanisms of cardiac nerve sprouting. We will use in-situ hybridization and immunocytochemical staining to detect NGF mRNA and the tenascin proteins in a canine model of MI. (2) Anatomical distribution and functional asymmeta of left and right stellate ganglia. We will study the differential electrophysiological effects of nerve sprouting of the left and right stellate ganglia. We will also use immunocytochemical techniques to demonstrate a differential anatomical distribution of nerves from these two ganglia. (3) Origin of nerves that sprout after MI. We will use recombinant lentivirus vectors (rLVs) to transfer fluorescent protein genes into the stellate ganglia. The cardiac nerve distribution will be determined by the location of positive immunocytochemical staining and fluorescent protein expression. (4) Induction of right stellate ganglion nerve sprouting by electrical current. We will use electrical current to induce cardiac nerve sprouting from the right stellate ganglion and to reduce the incidence of ventricular arrhythmia and SCD. These studies may lead to novel insights into the mechanisms of ventricular arrhythmogenesis after MI and may help develop new methods for arrhythmia control. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NITRIC OXIDE METABOLIC CONTROL IN PREGNANCY Principal Investigator & Institution: Hintze, Thomas H.; Professor; Physiology; New York Medical College Valhalla, Ny 10595 Timing: Fiscal Year 2003; Project Start 15-DEC-1993; Project End 31-DEC-2006 Summary: (provided by applicant): The cardiovascular adjustments that occur during pregnancy include chronic increases in cardiac output, falls in total peripheral vascular

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resistance and tachycardia. There is an upregulation of endothelial nitric oxide synthase in almost all vascular beds studied in the gravid female including skeletal muscle, kidney and utems or placenta. The upregulation of eNOS directly contributes to the fall in TPR which is not confined to the placenta. Many studies have investigated the role of NO in the control of vascular resistance or how NO may buffer vasoconstriction and that a defect in NO production may be involved in pre-eclampsia. Despite increasing evidence that NO also modulates mitochondrial metabolism and substrate uptake by the heart, i.e. prevents glucose uptake and facilitates fatty acid uptake, there are literally no studies that have investigated the role of increased eNOS in the control of substrate uptake and organ oxygen consumption at all. We have previously shown that NO by interacting with cytochrome oxidase in heart, kidney and skeletal muscle serves to maximize the ratio of oxygen consumed to external work performed ie. increases efficiency. We have also shown that when eNOS produces NO in the heart and elsewhere, glucose uptake is prevented. It is important to re-emphasize that pregnancy is characterized by increased eNOS gene expression and increased NO production in every vascular bed of the mother. Furthermore, glucose uptake by the mother is low even insulin insensitive and this is thought to increase the amount of glucose available for uptake through the placenta to support fetal metabolism, since the placenta does not take up fatty acids. In addition a small but significant number of mothers go on to have a post-partum cardiomyopathy often leading to heart transplantation, perhaps when adjustments that occur during pregnancy do not regress after parturition. Thus the focus of this competitive renewal application will be the role of NO in the control of oxygen and substrate use during pregnancy with particular reference to the heart and coronary circulation. In the first specific aim, we will examine the role of NO in the control or metabolism in aged eNOS KO mice. The second aim will focus on the role of NO in the pregnant eNOS KO mouse whereas the third specific aim will focus on the role of NO in cardiac glucose and oxygen uptake in the rat heart during pregnancy. Finally aim 4 will use chronically instrumented conscious pregnant dogs to address the role of NO in the control of cardiac function, substrate use and oxygen consumption during pregnancy and after parturition. For the first time we wilt perform a systematic mechanistic investigation into the role of NO in the control of cardiac oxygen and substrate use during pregnancy. These studies have direct application to the physiology of pregnancy and to the potential mechanisms resulting in post partum cardiac dysfunction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NO AND OXIDATIVE STRESS IN HUMAN MYOCARDIAL FAILURE Principal Investigator & Institution: Givertz, Michael M.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 15-AUG-1999; Project End 31-JUL-2004 Summary: The overall goal of this project is to determine the functional significance of myocardial nitric oxide (NO) and oxidative stress in humans with heart failure (CHF). Recent evidence suggests that NO is increased in failing human myocardium and may contribute to the pathophysiology of CHF. In addition, increased myocardial oxidative stress has been demonstrated in heart failure. In vitro studies indicate that reactive oxygen species (ROS) can exert direct toxic effects on the myocardium associated with impaired contractility, fetal gene expression and cell death. Moreover, antioxidants have been shown to attenuate the negative inotropic effects of ROS and prevent the development of heart failure in animal models. In left ventricular (LV) failure, the heart rate- mediated increase in contractility (force-frequency relationship) is attenuated, flat or even inverted. While the failure to increase contractility with tachycardia likely

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contributes to the reduced cardiac output response and exercise intolerance observed in patients with CHF, the underlying mechanisms are poorly understood. In Specific Aim 1, we will test the hypothesis that increased myocardial NO synthase (NOS) activity attenuates the force- frequency relationship in humans with LV failure by measuring the changes in the peak rate of rise of LV pressure (+dP/dt) that occur with increasing heart rates before and during intracoronary infusion of NG-monomethyl-L-arginine, an inhibitor of NOS. In Specific Aim 2, we will test the hypothesis that increased myocardial oxidative stress attenuates the force-frequency relationship in humans with LV failure by determining the force- frequency relationship before and during intracoronary infusion of the antioxidant ascorbic acid. Aims 1 and 2 are invasive protocols that will assess the acute functional significance of myocardial NO and oxidative stress in heart failure. In Specific Aim 3, we will test the ability of a novel, noninvasive system to detect acute changes in contractile state by measuring LV endsystolic elastance during atrial pacing tachycardia and intracoronary dobutamine infusion in patients with dilated cardiomyopathy. If we show that this new technology is able to measure changes in contractility in the catheterization laboratory, we will assess its ability to detect chronic changes in LV performance by measuring end-systolic elastance before and after therapy with antioxidants and/or anti- inflammatory agents in patients with systolic heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NOVEL CATHETER FOR TREATMENT OF VENTRICULAR TACHYCARDIA Principal Investigator & Institution: Curley, Michael G.; President; E.P., Ltd 35 Medford St, Ste 204 Somerville, Ma 02143 Timing: Fiscal Year 2002; Project Start 29-SEP-1999; Project End 31-AUG-2004 Summary: (provided by applicant): Sudden cardiac death kills 300,000 people in the United States yearly. More than half of these deaths are caused by arrhythmias including ventricular tachycardia. Radiofrequency ablation, which successfully treats supraventricular tachycardia, is not successful at treating ventricular tachycardia because conventional RF ablation catheters cannot treat a large enough volume of myocardium. In Phase 1 of this project, we have demonstrated the feasibility of salineenhanced ablation. We will have used infusion of warm saline through the myocardium (simultaneous with the application of radiofrequency or laser heating energy) to increase the tissue thermal transport by a factor of 20 or more. We have shown that this method can increase the volume of thermal lesions in myocardium by a factor of 12. These lesions are capable of treating the full thickness of the myocardium, and therefore show promise toward treatment of ventricular tachycardia. We will continue the development of this system during this Phase 2 project. Based on the Phase 1 results we will continue our development using saline enhanced radiofrequency ablations. We will develop a steerable catheter that will have a porous radiofrequency electrode at the tip, which will be inserted into the myocardium. The catheter will have a central lumen with an RF heater to heat the saline before injecting it into the myocardiurn. We will qualify this prototype catheter and system in preclinical studies of ventricular tachycardia in animal models at the Mayo Clinic and the Brigham and Women's Hospital. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ORTHOSTATIC INTOLERANCE IN AUTONOMIC NEUROPATHIES & POSTURAL TACHYCARDIA SYNDROME Principal Investigator & Institution: Low, Phillip A.; Professor; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002 Summary: The pathophysiology of orthostatic intolerance including orthostatic hypotension (OH) is poorly understood and hence its treatment has been unsatisfactory. The focus of this proposal is on the elucidation of mechanisms of orthostatic intolerance in the postural tachycardia syndrome (POTS) and neurogenic OH and develop pathophysiologically- based new treatment strategies. We will undertake a doubleblind, randomized, 4-way cross-over study of pyridostigmine in the treatment of neurogenic OH. This strategy of acetylcholinesterase inhibition to increase the safety factor of ganglionic transmission could improve OH without supine hypertension. A similar study will evaluate its efficacy in neurogenic POTS, where denervation is often also present. A blinded study will evaluate if sodium chloride will increase plasma volume and if urinary sodium secretion is a reliable surrogate measure of plasma volume. Seven studies will evaluate the pathophysiology of POTS. One is a power spectral analysis of autonomic rhythms that modulate the EEG. In particular, an ultralow frequency band (0.02-0.05 Hz) is reduced in POTS and may be of brainstem origin. One study will evaluate if carbonic anhydrase inhibition will improve cerebral perfusion and symptoms of POTS, since hypocapnia on head-up tilt is present. Two studies are focused on the venous capacitance bed in the legs and abdomen. One evaluates if the capillaries are excessively leaky, using plethysomographic techniques. The other evaluates, using a modified G- suit (compresses specific venous compartments), which capacitance beds are most responsible for orthostatic intolerance. Techniques are now available to study the systemic )beat-to-beat BP and impedance methodology), mesenteric (superior mesenteric blood flow ultrasonography), cerebrovascular (transcranial doppler) circulations simultaneously, and sympathetic discharges can be directly measured using microneurography. The hypothesis that pre-ganglionic lesions cause a different pattern of autonomic vascular involvement to post- ganglionic lesions will be tested. Finally, the independent predictors of auto-regulatory adaptation of the cerebrovascular circulation in neurogenic OH will be studied. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ORTHOSTATIC INTOLERANCE IN CFS Principal Investigator & Institution: Freeman, Roy; Associate Professor of Neurology; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2003; Project Start 01-FEB-1998; Project End 30-JUN-2007 Summary: (provided by applicant): The chronic fatigue syndrome (CFS) is a common disorder of unknown cause that incapacitates young individuals in their most productive years. There is evidence that orthostatic intolerance may play a role in the fatigue of patients with CFS. The broad long-term objectives of the project are to delineate the pathophysiology and pathogenesis of orthostatic intolerance in the chronic fatigue syndrome (CFS); to investigate the role of orthostatic intolerance in producing the symptoms of CFS; to use this information to institute physiologically appropriate therapeutic interventions; and thereby decrease the symptoms of fatigue. The Specific Aims of the application are to enhance cardiovagal outflow with low dose atropine and Iosartan and examine the cardiovascular response to orthostatic stress; to characterizing sympathetic nervous transduction to vascular resistance in the lower limbs and

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characterize the sympathetic responses in the lower limbs to orthostatic stress; to measure transcapillary interstitial fluid filtration during orthostatic stress determine the relationship between capillary filtration and plasma volume; and characterize cerebral blood flow, systemic pressure maintenance, postural tachycardia and parasympathetic outflow. We will assess arterial baroreflex gain by measuring the heart rate and muscle sympathetic nerve activity response to pharmacological provocations; sympathetic transduction by relating muscle sympathetic nerve activity to peripheral resistance; plasma volume using the Evans Blue dye method; venous compliance using venous occlusion plethysmography; and cerebral blood flow velocity with transcranial Doppler. These measures, which comprise the elements of orthostatic tolerance, will be compared with healthy controls selected to match the gender, age and level of physical activity of the subjects. The relationships between these variables and role of covariates such as the level of physical activity and psychiatric state, determined with standardized instruments, will be analyzed using multivariate statistics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OVARIAN HORMONE METABOLITES & NEURAL CIRCULATORY CONTROL Principal Investigator & Institution: Heesch, Cheryl M.; Associate Professor; Veterinary Biomedical Sciences; University of Missouri Columbia 310 Jesse Hall Columbia, Mo 65211 Timing: Fiscal Year 2002; Project Start 01-SEP-1985; Project End 31-DEC-2003 Summary: (Adapted from the application) Normal pregnancy is associated with a 40% increase in blood volume and cardiac output, slight tachycardia, and a decrease in arterial blood pressure. Enhanced baroreflex sympathoinhibition and attenuated sympathoexcitation have been reported in pregnant animals, although the mechanisms have not been well defined. The primary metabolite of progesterone, 3-alpha-hydroxydihydroprogesterone (3-alpha-OH-DHP), which is elevated in pregnancy, is a potent positive modulator of central nervous system (CNS) inhibitory GABA-A receptors. Exogenous administration of 3-alpha-OH-DHP to virgin animals mimics the effects of pregnancy: sympathoinhibition is enhanced and sympathoexcitation is attenuated, most likely through a CNS mechanism. Importantly, blocking the formation of endogenous 3alpha-OH-DHP in pregnant reverses the attenuated sympathoinhibition. Previous studies focused mainly on enhanced arterial baroreflex sympathoinhibition. In the current proposal, experiments are designed to evaluate mechanisms for the attenuation of sympathoexcitatory responses (likely not arterial baroreflex mediated). The general hypothesis is to be tested that attenuated sympathoexcitation during pregnancy is associated with GABAergic mechanisms in central nervous system sites involved in regulation of cardiovascular function. Three possibilities will be evaluated: Increased inhibitory influences from peripheral receptors other than arterial baroreceptors, increased inhibitory influences from the CNS, and decreased excitatory effects in the rostral ventrolateral medulla (RVLM, brainstem site of cardiovascular sympathetic premotor neurons). Experiments in virgin and pregnant rats will evaluate the CNS expression of Fos protein in identified neuronal populations involved in central cardiovascular control following manipulations which normally increase or decrease efferent sympathetic nerve activity. Efferent sympathetic nerve activity will be recorded in other experiments in which inhibitory afferent inputs, CNS inhibitory influences, and excitatory inputs to the RVLM will be altered. Understanding the mechanism for suppressed sympathoexcitatory responses in normal pregnant animals will have

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important implications for hypertensive disorders or pregnancy which are associated with exaggerated sympathoexcitatory responses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PARTICLE-INDUCED CARDIAC EFFECTS IN SENESCENT MICE Principal Investigator & Institution: Tankersley, Clarke G.; Assistant Professor; Environmental Health Sciences; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 31-DEC-2008 Summary: (provided by applicant): Plausible biological mechanisms remain elusive to explain the association between daily fluctuations in air pollution and increased mortality rates. Specifically, airborne particulate matter (PM) has been identified as the constituent of air pollution that is most culpable in correlating with increased mortality rates. Pathophysiologic mechanisms leading to tachycardia and bradycardia appear potential processes that increase PM-induced risk of mortality in humans and animal models. Because epidemiology studies also identify aging as a risk factor, we developed a unique model to define risk associated with terminal senescence based on a series of pathophysiological assays. HYPOTHESIS: Senescent-dependent changes in the neurohumoral regulation of the heart during PM exposure manifest acute instability in cardiac function resulting from imbalances in the autonomic nervous control and altered atrial natriuretic peptide regulation. Specific aim 1 characterizes specific pathophysiologic variables associated with loss of homeostasis in senescent mice of different inbred mouse strains. Specific aim 2 determines the interactive effects of terminal senescence and acute PM exposure on heart rate regulation and cardiac function. Here, we postulate that only terminally senescent animals are susceptible to the acute cardiac effects of PM exposure. Specific aim 3 determines the interactive role of innate susceptibility factors in acute PM-induced imbalances in autonomic neural regulation of heart rate, blood pressure and cardiac function. The focus of this aim considers PM-induced cardiac functional changes owing to genetic susceptibility factors. Specific aim 4 tests whether senescent-dependent susceptibility to PM-induced cardiovascular dysfunction evolves from adverse modifications in atrial natriuretic peptide (ANP) regulation. In the final aim, cardiac mechanisms surrounding right ventricular function and pulmonary hypertension are considered important factors in PM-induced susceptibility. The interaction between aging and PM exposure obliterates the cardioprotective effects of ANP leaving the heart acutely susceptible to instability. In summary, the proposed studies are significant because they represent a multidisciplinary approach that will advance our understanding of the adverse cardiac health effects of air pollution exposure in the elderly Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PH III: AZIMILIDE CONTROLLED TRIAL Principal Investigator & Institution: Bahnson, Tristram D.; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PHYSIOLOGIC BENEFITS OF BIVENTRICULAR PACING IN CHF Principal Investigator & Institution: Hamdan, Mohamed H.; Associate Professor of Internal Medicine; Internal Medicine; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 20-SEP-2000; Project End 31-AUG-2004 Summary: (The applicant's description verbatim): Acute biventricular (BV) pacing has been shown to result in hemodynamic improvement in patients with left ventricular dysfunction. Based on these studies, the effect of long term BV pacing on exercise tolerance and quality of life are being assessed in large prospective trials. What remains unknown are the effects of BV pacing on sympathetic activity, a known predictor of cardiac mortality, and on the incidence of ventricular arrhythmias. We hypothesize that in patients with LV dysfunction 1) BV pacing decreases sympathetic activity compared to intrinsic conduction in the presence of intraventricular conduction delay 2) BV and LV pacing improves hemodynamics and decreases sympathetic activity compared to right ventricular pacing 3) BV pacing decreases the inducibility of ventricular arrhythmias and 4) that this latter effect is due to preexcitation and prolongation of the coupling interval in the "slow" zone of the tachycardia circuit. To test these hypotheses, consecutive patients referred to the arrhythmia section at the Dallas VAMC with LV dysfunction and an indication for electrophysiologic evaluation will be enrolled in the study. During phase 1 and 2, arterial pressure, central venous pressure and muscle sympathetic nerve activity using microneurography will be recorded during sinus rhythm, atrial pacing (in patients with a QRS greater than 150msw) and atrialventricular pacing (RV, LV or BV). Pacing will be performed at a rate 10 beats faster than sinus rhythm. During phase 3 and 4, we will assess the effect of BV pacing on the inducibility of ventricular arrhythmias and the associated electrophysiologic changes. The outcome of this study will have a great impact on our management of patients with congestive heart failure. A reduction in sympathetic activity, demonstrated first with acute BV pacing and later with long term pacing, may have a beneficial effect on mortality. Similarly, a reduction in inducibility of ventricular arrhythmias, if present with long term pacing, may have an impact on the survival and on our management of patients with implantable defibrillators and frequent shocks. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PREVENTION OF INTRA ATRIAL REENTRANT TACHYCARDIA AFTER STAGED FONTAN REPAIR Principal Investigator & Institution: Law, Ian H.; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PROGNOSTIC VALUE OF REPOLARIZATION MEASURES Principal Investigator & Institution: Green, Larry S.; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2002 Summary: This project is a clinical study of repolarization factors that predict arrhythmia risk. It consists of two related subprojects that both focus on quantitative measures of repolarization that will lead to clinically useful assessment of arrhythmia

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risk. The techniques used to measure repolarization will be derived from those developed in the animal experimental studies in Project 4 and they will then be applied to studies that evaluate therapeutic interventions in arrhythmia prone patients. Hence this project plays a pivotal role in linking the technical developments in experimental studies to the direct clinical application of monitoring and will prospectively evaluate repolarization abnormalities in over 2000 post-myocardial infarction patients using multi-read electrocardiography. Project 5.2 will study the role of the autonomic nervous system on repolarization in a group of patients with documented ventricular tachycardia. One study will measure repolarization changes leading up to arrhythmic events by means of QT interval, ARIs, and T- wave amplitudes measured from Holter ECGs. The second wave will induce repolarization changes by means of head-up tilt and compare the ECGs. The second study will induce repolarization changes by means of head-up tilt and compare the resulting repolarization change to those observed prior to spontaneous episodes of ventricular tachycardia. Success in these studies would provide robust electrocardiographic screening methods for arrhythmic sudden cardiac death. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROSPECTIVE ASSESSMENT AFTER PEDIATRIC CARDIAC ABLATION Principal Investigator & Institution: Van Hare, George F.; Pediatrics; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 01-MAY-1998; Project End 30-APR-2004 Summary: (Adapted from Investigator's Abstract) Radiofrequency catheter ablation is a catheterization laboratory technique for the cure of cardiac arrhythmias, which has become common in pediatric cardiology practice. Recent analyses have suggested that ablation therapy is more cost-effective compared not only with surgery, but also with antiarrhythmic medication. Despite a good initial success rate of the technique, and a low initial complication rate, there is concern about possible long-term effects with the technique in the pediatric age group. There are reports not only of damage to cardiac valves, but also the development of new arrhythmias, including sudden death, as a result of ablations in children. Recurrences are observed frequently following initially successful procedures. Finally, there are animal data to suggest that immature myocardium is more prone to severe damage as a result of ablation procedures. Few, if any, data exist to support the long-term safety of these ablation techniques in children. Therefore, before ablation therapy becomes the standard approach in children, it is important to carefully assess the long-term risks in this patient group. The application presents plans to conduct a multi-center, prospective, 5-year study to evaluate children undergoing catheter ablation at pediatric centers in North America. The collection of these data is intended to provide the following information: 1) the incidence of serious cardiac damage as a result of ablation; 2) the incidence and time course of recurrence after initially successful ablation; and 3) the incidence of proarrhythmia following ablation. A total of 450 pediatric patients will be enrolled prospectively and evaluated both before ablation of supraventricular tachycardia and at intervals following ablation with clinical history and examination, electrocardiogram, 24-hour Holter monitor, and echocardiogram, with non-invasive studies read by outside consultants. In addition, a complete Registry of pediatric patients undergoing ablation at the participating centers will be established to allow comparisons with the study group and to provide population estimates of success and complication rates. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INFARCTION

PURKINJE-MYOCARDIAL

REENTRY

IN

ISCHEMIA

AND

Principal Investigator & Institution: Pollard, Andrew E.; Associate Professor; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2003 Summary: The contribution of the heart's specialized conduction system to arrhythmia initiation is not completely understood. While Purkinje fibers are considered a potent source for the initiating extrasystoles in focal and reentrant ventricular arrhythmias, recent suggests a contribution of Purkinje-myocardial reentry to polymorphic tachycardia that can precede fibrillation and sudden death. Our main objective is to investigate how reentrant circuits distribute between the peripheral conduction system and overlying myocardium during early cycles of sub-endocardially- induced ventricular arrhythmias. We believe those circuits circumscribe functional centers that are primarily located on the peripheral conduction system-myocardial interface, where the two components are weakly coupled via the system of discrete Purkinje-ventricular junctions (PVJs). We hypothesize this arrangement establishes peripheral conduction system and myocardial wavefronts that are out of phase with one another, which places critical importance about the ability of premature action potentials to propagate from peripheral conduction system to myocardium, i.e. antegrade PVJ conduction, for reentry maintenance. Antegrade PVJ conduction is inherent discontinuous because the myocardium imposes a large electrical load on peripheral conduction system. Experiments to test this hypothesis will use 1056-channel electrical mapping from perfused rabbit right ventricular free wall surfaces. Companion stimulations will incorporate membrane equations for ionic currents into detailed grids replicating the interface. The project has two aims. The first aim is to establish the relationship between antegrade PVJ PVJ conduction and subendocardially induced ventricular arrhythmias in macroscopically normal hearts. The second aim is to correlate regional acute ischemia and healing myocardial infarction with peripheral conduction system participation during subendocardially induced ventricular tachycardia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RANDOMIZED CLINICAL TRIALS FOR PEDIATRIC HEART DISEASE Principal Investigator & Institution: Saul, J P.; Pediatrics; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 31-AUG-2006 Summary: (provided by the applicant) The Children?s Heart Program of South Carolina is a statewide consortium of pediatric cardiologists, who care for 90% of the 3.7 million residents in the state. This consortium has all the critical elements for a center in the proposed research network: adequate patient volume, clinical research infrastructure, a track record of subject enrollment, and a demonstrated dedication to hypothesis driven clinical research. The applicant center, MUSC, is the tertiary referral center for the Children?s Heart Program. Current MUSC faculty have participated as PI?s in a total of 20 multicenter clinical trials or registries (10 open, 2 under IRB review). The PI of this application has been the lead investigator nationally in 4 of the 20. These protocols range from industry sponsored drug or device trials, to an NIH sponsored drug trial for fetal heart block, to an NIH prospective registry. The faculty also currently runs 11 local clinical research protocols. Participation in all of these protocols is supported by a dedicated pediatric cardiac research support group with 2 full time RN coordinators and

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an additional RN FTE. The combined resources of high volume and strong research infrastructure have enabled the PI?s at MUSC to be one of the top 2 subject recruiters in 6 of the 18 completed or active multicenter studies. As requested, the proposal contains a short-term and a long-term protocol. Short-Term. Randomized Trial of Aortopulmonary Collateral Coil Occlusion Prior to Fontan. Multiple factors influence morbidity and mortality for single ventricle patients undergoing Fontan operation. One considered recently is the presence of APC?s. However, multiple retrospective studies have failed to clearly delineate the role of APC?s or their optimum management. This protocol will prospectively evaluate the role of APC?s in postoperative Fontan hemodynamics and morbidity, and determine the importance of preoperative coil embolization in their management. Long-Term. Randomized Trial of Amiodarone vs Cooled- Tip Catheter Ablation for Treatment of Recurrent Intra-atrial Reentry Tachycardia (IART) in Patients with Congenital Heart Disease. IART, the single largest cause of morbidity late after repair of congenital heart disease, is often life-threatening, frustrating to treat and has no clearly superior therapy. This protocol will prospectively compare the most successful medical and catheter therapies for IART. The primary endpoint during a minimum of 2 years follow-up will be IART recurrence after successful ablation, or after drug loading and cardioversion. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REENTRANT MONOLAYERS

ACTIVITY

IN

CULTURED

CARDIAC

CELL

Principal Investigator & Institution: Tung, Leslie; Associate Professor; Biomedical Engineering; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 08-AUG-2001; Project End 30-JUN-2005 Summary: Reentrant mechanisms play a primary role in many types of arrhythmias, including tachycardia and flutter in the atria, ventricles, and atrioventricular node. Reentry may involve anatomical pathways, or it may be functional, with leading circle, figure-eight, anisotropic, and spiral wave variants. The primary goal of this research is to establish a simple and reproducible cultured cell model for the study of anatomical and functional cardiac reentry under well-controlled experimental conditions. We propose to use voltage-sensitive dyes and high- resolution optical mapping to monitor reentrant activity in monolayers of neonatal rat heart cells. A detailed computational model will be verified against experimental data drawn from action potential and intracellular calcium measurements, and their restitution and rate-dependent behavior in this experimental model. The computational model will be used to identify the ionic currents and biophysical mechanisms responsible for reentry behavior. New microfabrication and surface chemical approaches will also be used to develop patterned substrates that direct the growth of cells in the monolayers. The combined experimental and computational approach that is proposed in this study will permit a detailed quantitative analysis and dissection of tissue behavior down to the cellular level. We will, 1) formulate an experimentally-based, biophysical model of the neonatal rat cardiac cell monolayer 2) characterize reentry in confluent monolayers of cultured neonatal rat heart cells, and 3) determine the electrophysiological properties and role of the core of the reentrant circuits. Issues of critical mass, excitable gap, and leading circle vs. spiral wave reentry will be addressed. These aims will establish the cultured cell monolayer as a well-controlled, versatile and quantitative experimental model for basic studies of reentry- based arrhythmias. The simplicity and flexibility of this model system provides numerous advantages over existing tissue models of reentrant

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arrhythmia. Moreover, the cell culture is well suited for studies involving pharmacological, genetic and molecular manipulation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF LATE INWARD CURRENT IN HUMAN HEART FAILURE Principal Investigator & Institution: Makielski, Jonathan C.; Professor of Medicine and Physiology; Medicine; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 26-SEP-2000; Project End 31-AUG-2004 Summary: Action potential prolongation in heart failure may contribute to the generation of arrhythmia in heart failure. The action potential could be prolonged either by decreasing outward currents or by increasing inward currents during the plateau phase. Nearly all studies of electrical remodeling underlying this prolongation have emphasized decreased outward current by down-regulation of potassium channels. Recent studies, including our own preliminary results, show an increase in late inward sodium current in animals models of heart failure, and we show in this application for the first time that it is also significantly increased in human heart failure. We propose to study this sodium current in ventricular cells from normal and failing hearts from a canine tachycardia pacing model of heart failure, and for normal and failing human hearts. Using whole cell and single channel voltage clamp techniques we will determine the amplitude and kinetics of this current under conditions important for physiological and pathophysiological interpretation including Ca and Na dependence, temperature dependence, regional and transmural distribution and heterogeneity, and antiarrhythmic drug block. We will also study the effect of sodium channel block on action potential duration for cells from epi, endo, and mid-myocardium. The potential mechanisms for the increase in late current in heart failure will be studied. These include alpha subunit isoform switching or beta subunit down-regulation, altered regulation by cell signaling pathways (alpha and beta adrenergic, endothelin and angiotensin), and other mechanisms such as altered free fatty acids, cytoskeleton, and nitric oxide regulation. These studies will produce the first detailed data on late sodium currents in humans and its regulation, and at the same time investigate the mechanism and the significance for this current in the electrical remodeling underlying arrhythmogenesis in heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REMODELING OF GAP JUNCTIONS IN REENTRANT CIRCUITS Principal Investigator & Institution: Wit, Andrew L.; Professor; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2002 Summary: Description (Adapted from Applicant's Abstract) The applicant's have shown that structural remodeling of gap junctions, characterized by increased connexin43 along the lateral myocyte membranes, occurs in reentrant circuits that cause ventricular tachycardia in canine infarcted hearts. This discovery has led to this proposal in which the objectives are; 1) to determine the role of gap junction structural remodeling and altered gap junction physiology (electrophysiological remodeling) that occur as a consequence of myocardial infarction, in causing slow an discontinuous conduction necessary for reentrant excitation and 2) to determine how remodeled gap junctions in reentrant circuits affect the response of ventricular arryhthmias to anti-arrhythmic

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drugs. To accomplish these objectives, a canine infarct model of reentrant circuits in the epicardial border zone will be investigated with different methodologies designed to elucidate structured, electrophysiology and pharmacology of gap junctions. These include in vivo activation mapping, immunolocalization of connexin proteins, and measurements of transjunctional conductances in myocyte cell pairs from the infarct border zone. The different methods will be integrated to investigate the following questions. Does the pattern of structural gap junction remodeling determine the size, shape and location of reentrant circuits and the kinds of arrhythmias which occur? How does gap junctional remodeling of influence propagation of electrical activity i.e. does it cause discontinuous conduction and conduction block? Is structural remodeling associated with reduction in transjunctional conductance that contributes to slow conduction? Are remodeled gap junctions more sensitive to changes in intracellular calcium, possibly explaining the occurrence of conduction block during rapid heart rates or after pharmacologically increasing the L-type calcium current? Does an increased sensitivity of remodeled gap junctions to pH play a role in causing slow activation and conduction in regions with poor gap junction coupling? And, are remodeled gap junctions a sensitive target for drug induced termination of reentrant arrhythmias? When the answers to those questions are obtained, the applicants assert that they will have a comprehensive picture of the electrophysiological and pharmacological consequences of gap junctional remodeling in ischemic heart disease. Gap junctions will be shown to be an important target for drug development to prevent sudden arrhythmic death. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RENAL DENERVATION IN ORTHOSTATIC INTOLERANCE Principal Investigator & Institution: Biaggioni, Italo; Professor of Medicine and Pharmacology; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SELECTIVE MODULATION OF THYROID RECEPTOR ACTION Principal Investigator & Institution: Baxter, John D.; Professor and Director of Medicine; Diabetes Center; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 31-DEC-2007 Summary: (provided by applicant): Nuclear receptors (NRs) regulate numerous medically important processes in humans and include receptors for thyroid (TH) and steroid hormones, vitamin D, retinoids and prostaglandins. Selective modulation of NR function is an emerging concept in NR ligand design. While there is progress, many concepts are poorly understood. Many TH actions would have medical utility in reducing cardiovascular disease risk. TH stimulates metabolism, promotes weight loss, and lowers plasma levels of cholesterol, triglycerides, and lipoprotein (a). However, TH benefits are offset by deleterious influences, including effects on heart that include lifethreatening tachycardia and arrhythmia. It is desirable to block TH in hyperthyroidism, but current blockade by inhibiting TH production is slow in onset. Thus, it is important to identify selective TR modulators (STRMs). We used structure-activity profiling and TR X-ray crystal structures for designing: (i) selective TR modulators (STRMs) that preferentially bind the TRbeta-form, and may be prototype drugs for treating obesity

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and lipid disorders; and (ii) novel TR antagonists and partial agonists. Preliminary studies indicate that these ligands could have further potentially useful selective properties, including differences in cell uptake, activation and suppression of individual promoter elements, and abilities of their activities to be regulated by coactivators and corepressors. In the proposed studies we plan to examine properties of a spectrum of ligands to better understand their activities. We will determine effects of individual STRMs on: (i) TR conformation; (ii) TR interactions with cofactors in cell-free conditions and in cells; (iii) individual TR activation functions; (iv) TR-mediated gene expression at model promoters; and (v) gene expression profiles in intact cells. The information obtained will be integrated to provide profiles for individual and combinatorial features that may be ultimately exploited for rational design of ligands with more desirable profiles than either pure agonists or antagonists. This study will expand our understanding of selective TR modulation in specific and NR action in general. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SOTALOL IN CHILDREN WITH TACHYARRHYTHMIAS Principal Investigator & Institution: Triedman, John K.; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SPECIALIZED CENTER OF RESEARCH IN SUDDEN CARDIAC DEATH Principal Investigator & Institution: Marban, Eduardo; Professor; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 20-JAN-1995; Project End 31-DEC-2004 Summary: Sudden cardiac death accounts for 30-50% 0f heart failure mortality. This proposal, which is the continuation of an existing SCOR program in Sudden Cardiac Death, investigates the biological basis of altered excitability in heart failure and how predisposes to fatal ventricular arrhythmias. The SCOR is motivated by the following central hypothesis: Abnormalities of ionic currents and calcium handling render repolarization unstable in failing myocardium, increasing spatiotemporal variability of repolarization and predisposing patients with heart failure to sudden death. This hypothesis has been tested and validated extensively in the first five years of the program. We now propose to probe the biological basis of the abnormal repolarization, with a view to developing novel strategies for the identification of patients at high risk. Our program features a central animal model (pacing tachycardia canine heart failure) as well as tissue and myocytes from explanted human hearts. The program consists of five projects and five cores. Project 1, directed by Eduardo Marban, will use gene transfer and cell fusion to dissect the molecular determinants of cardiac repolarization. Project 2 focuses on L- type calcium channel inactivation. Project 2 focuses on L-type calcium channel inactivation under the leadership of David Yue. Project 3, directed by Gordon Tomaselli, investigates the relative roles of voltage- dependent and calciumdependent mechanisms in the action potential prolongation of heart failure. Project 4 probes the neurohumoral modulation of electromechanical remodeling in heart failure, under the directorship of David Kass. Project 5, led by Ronald Berger, examines temporal QT interval variability as a predictor of severe arrhythmias and sudden cardiac death in patients. The five cores will provide support in the following areas:

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administrative matters, molecular genetics and vectors, animal models and cells, human cells and tissue, and quantitative modeling. The program in its first five years has been highly productive and interactive. The proposed continuation combines existing strengths with new approaches in a strongly synergistic manner. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STRUCTURAL GENOMICS OF NOREPINEPHRINE TRANSPORTERS Principal Investigator & Institution: Blakely, Randy D.; Associate Professor; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): The antidepressant-sensitive norepinephrine (NE) transporters (NETs) constitute the major mode of synaptic inactivation of NE. Recent clinical genetic studies by our groups identified a coding mutation, A457P, in one NET allele of a proband with Orthostatic Intolerance (OI) presenting with reduced NE clearance, increased spillover and reduced intraneuronal NE metabolism. The A457P mutation was found to track with measures of postural tachycardia in the proband?s family and to correlate with altered synaptic NE metabolism. In Specific Aim 1, we propose to ascertain the functional impact of the A457P and other identified NET coding mutations in terms of transport and efflux, transporter trafficking and surface expression using heterologous expression systems. Evidence will be sought to support a dominant-negative interaction between mutant and wildtype subunits and whether homomultimeric complexes support NET function. In Specific Aim 2, we propose to extend our genetic evaluation of NET deficiency to evaluate additional subjects with OI and cardiomyopathy (CM) using high-throughput gene scanning techniques. These studies will focus on the NET coding exons and splice junctions and also include a recently identified intronic region that plays a critical role in NET gene expression. Methods will be implemented to allow for an evaluation of altered NET protein in biopsies tissue. Finally, attention and mood are dependent on proper noradrenergic signaling in the CNS and symptoms are present in our A457P probands indicating attention deficit, anxiety and hyperarousal. Thus, we propose in Specific Aim 3 to examine NET alleles with primary diagnoses of attention-deficit hyperactivity disorder (ADHD), attentional deficit (ADD) subtype and Major Depression, melancholic subtype, which is characterized by hyperarousal and anxiety. We will select subjects for analysis in both cases on the basis of comorbid tachycardia. Together these studies offer an opportunity for a better understanding of the molecular and behavioral manifestations of genetic NET variation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SUBCUTANEOUS MONITOR/ALARM FOR CARDIAC ARREST Principal Investigator & Institution: Arzbaecher, Robert C.; Professor and Director; Aj Medical Devices, Inc. 155 N Harbor Dr, Ste 2804 Chicago, Il 60601 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 30-MAY-2004 Summary: It is estimated that 220,000 people suffer cardiac arrest each year in the US, of whom only 10,000 survive to hospital discharge. The number of survivors could increase 10-fold if paramedical attention and/or defibrillation were available within a new minutes of the attack. It is the goal of our company to develop and deploy new and innovative technology that improves survival of cardiac arrest by lessening the time to treatment. This is a proposal to design, develop, and test the feasibility of an implanted monitor that notifies bystanders and emergency medical services (EMS) of an incipient

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cardiac arrest and/or acute myocardial ischemia. Such notification can shorten materially the time to defibrillation of most witnessed, and all unwitnessed, episodes of cardiac arrest, thereby improving survival manyfold. The tiny device will automatically detect the lethal event and signal transcutaneously to a cellphone-size purse, pocket, belt-worn or night stand unit which gives voice instructions to bystanders, spouse, or other witnesses and transmits victim location to the nearest EMS. Candidates for the implanted device are those readily identifiable cardiac patients whose medical condition and/or history puts them at particularly high risk of cardiac arrest. PROPOSED COMMERCIAL APPLICATIONS: The monitor/alarm will address the problem of 220,000 cardiac arrests a year of which only 3-5% presently survive. An implanted monitor/alarm could speed life saving rescuers to a victim of cardiac arrest, summon EMS automatically, and provide instant victim location. The US market for such a device could exceed 100,000 units, as our ability to define the population at risk improves. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SUBSTRATE TACHYCARDIA

MAPPING

&

ABLATION OF

VENTRICULAR

Principal Investigator & Institution: Reddy, Vivek Y.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 30-JUN-2007 Summary: (provided by applicant): In patients with coronary artery disease at risk for sudden cardiac death, malignant ventricular tachycardia (VT) is treated with a combination of implantable defibrillators and antiarrhythmic drugs. While effective in preventing sudden cardiac death, this strategy is plagued with medication side-effects and toxicities, and device related iatrogenic complications. The ideal treatment for VT would be eradication of the arrhythmia. This can be accomplished with greater than 90% efficacy through surgical resection of the infarcted arrhythmogenic tissue; however, this is an open surgical procedure associated with significant morbidity and mortality. Radiofrequency (RF) catheter ablation is an effective less-invasive alternative, but is largely limited to hemodynamically-tolerated VT-which accounts for less than 10% of all VT. However, the approach to catheter ablation of VT is undergoing a paradigm shift. Instead of trying to precisely identify the critical portions of the VT circuit during tachycardia, "substrate mapping" is performed in sinus rhythm to identify the arrhythmogenic tissue. Then, a probabilistic approach to catheter ablation is undertaken using strategically-placed linear RF lesions. While this strategy has proven to be successful in small non-randomized studies, the safest and most efficacious method to deliver the RF ablation is not known. Also, the role of substrate ablation in the primary prevention of ICD shocks is unknown. We now propose to conduct prospective randomized clinical trials: a) comparing the standard non-irrigated to the salineirrigated RF ablation catheter for substrate-mapping and ablation in the treatment of patients with multiple ICD shocks (the THERMO COOL IDE trial), and b) examining the role of substrate-mapping and RF ablation in the primary prevention of ICD shocks (the SMASH-VT trial). Furthermore, the abilitv of a new 3-dimensional mapping system to rapidly identify the arrhythmogenic substrate will be examined in a porcine model of healed myocardial infarction with inducible VT. Finally, using this advanced mapping system to identify the substrate, the effect of catheter-mediated cryoablation will be compared to RF ablation using a saline-irrigated catheter on the inducibility of VT in this animal model system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SURGICAL TREATMENT OF CARDIAC ARRHYTHMIAS Principal Investigator & Institution: Boineau, John P.; Medical Science Service; Surgery; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 08-AUG-1983; Project End 31-JUL-2003 Summary: This renewal application requests five years' support for work now in continuous progress for over 15 years at Washington University. Dr. John Boineau, the new PI, has replaced Dr. James Cox, the former P1, who transferred to Georgetown University Hospital. Dr. Cox remains as a special consultant. The broad aims continue to be the direct or surgical ablation of cardiac arrhythmias. The emphasis of the current renewal is focused upon the development of a new procedure, the radial incisions approach (RIA), to eradicate atrial fibrillation (AF) and restore atrial transport function and is directed primarily toward patients undergoing surgery for valvular or ischemic heart disease. Conventional valve or CABG surgery does not eliminate and may not prevent AF in these patients. The availability of an effective means of eradicating this arrhythmia in these patients at the time of surgery would permit control of rate and rhythm, limit embolic stroke, and improve cardiac performance, outcome, and the quality of life. Whereas the Maze and RIA assume randomly distributed and changing reentry which are eliminated without prior activation mapping, new data indicate that some forms of AF result from (spatially) stable reentry which can be identified by new mapping methods and focally ablated. Thus, a second project is directed toward map guided, focal cryoablation of AF. This could be performed off bypass as a more limited and rapid alternative to the more extensive and (bypass) time consuming RIA procedure. A third project is targeted at prevention and correction of postoperative atrial flutter (AFL) after the Fontan operation in congenital heart patients or after lung transplant surgery. Studies will be performed in both realistic animal models with atrial enlargement and patients with AF and AFL and will center about the use of new automated, 3-D mapping techniques and rapid numerical analysis of potentials recorded simultaneously from to 512 electrodes during the arrhythmias. Preliminary observations indicate that the proposed studies are feasible, will provide new information regarding the different mechanisms of AF and AFL that are related to atrial enlargement and/or atrial surgery, and this data will be used to develop the new surgical ablation techniques to control or prevent these arrhythmias. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SWELLING ACTIVATED CURRENTS AND MYOCYTE VOLUME IN CHF Principal Investigator & Institution: Baumgarten, Clive M.; Professor of Physiology; Internal Medicine; Virginia Commonwealth University Richmond, Va 232980568 Timing: Fiscal Year 2004; Project Start 30-SEP-2000; Project End 31-JAN-2005 Summary: (the applicant's description verbatim): Congestive heart failure (CHF) induces significant changes in cardiac myocyte size. Increased myocyte volume (hypertrophy) ultimately requires intracellular accumulation of osmolytes and water. Intracellular osmolarity is regulated in myocytes by multiple mechanisms, including transmembrane flux of ions through channels that are sensitive to changes in cell volume. We discovered that one of these ionic currents, the cell swelling-activated Clcurrent (IC,lswell) is chronically activated under isosmotic conditions in ventricular myocytes from dogs with tachycardia-induced and rabbits with aortic regurgitationinduced CHF. Furthermore, we showed that the activity of ICl,swell and cell volume in CHF and control myocytes were regulated by protein kinase C (PKC) and protein

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phosphatases thought to control phosphorylation of ion channels responsible for lCl,swell. The overall objective is to understand how Icl,swell and cell volume are regulated in volume and pressure overload models of CHF and how hormonal and autocrine-paracrine factors implicated in the genesis of CHF contribute to this regulation. The effects of catecholamines, autocrine-paracrine factors including angiotensin II and cardiotrophin-1, and selected growth factors on Icl,swell and cell volume will be examined. Intracellular signaling pathways, including protein kinase C, tyrosine kinases, mitogen-activated protein kinases, and phosphatases, will be examined to evaluate their influence on lCl,swell and myocyte volume. Perforated patch voltage clamp and digital video microscopy will be used concurrently to quantify ionic currents and their effect on cell volume. Single myocytes isolated acutely from either sham operated or CHF animals will be studied because these cells better reflect the in vivo state during CHF than do cell culture models. Because no single model of CHF fully represents clinical CHF, pressure, tachycardia, and volume overload models of CHF will be used. Where appropriate, the effect of interventions on cell signaling pathways will be confirmed with western blot with phospho-antibodies. The following questions will be addressed: 1. Are lCl,swell behavior and its effect on myocyte volume different in pressure than volume overload CHF? 2. Is Icl,swell activated prior to onset of clinically apparent CHF in pressure and volume overload models? 3. Are lCl,swell and myocyte volume regulated by autocrine-paracrine factors that are important in the genesis of CHF? 4. Do intracellular signaling pathways that are important in CHF influence lCl,swell and myocyte volume? Knowledge of swelling-activated ion currents and how they influence myocyte volume in CHF may provide important insights into the pathophysiology of tachyarrhythmias and contractile and diastolic dysfunction that occur in CHF. Further, this work may lead to new approaches to treat or prevent CHF and thereby, reduce the morbidity and mortality of this common disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SYMPATHETIC TACHYCARDIA

RESPONSES

DURING

VENTRICULAR

Principal Investigator & Institution: Weiss, James N.; Kawata Professor Med. & Physiol.; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002 Summary: Objective. The longterm goal of this project is to investigate further the role of the sympathetic nervous system in determining sudden cardiovascular death during ventricular tachycardia in humans, and thereby improve survival. Background. In humans, sympathetic nerve activation during ventricular tachycardia is an important determinant of hemodynamic stability during ventricular tachycardia, independent of ventricular function and tachycardia rate. In animal models, the arterial baroreflex and cardiopulmonary baroreflex have important, yet opposing, effects on sympathetic activation during ventricular tachycardia. The relative contributions of these control mechanisms in humans is unknown. Specific Aims. The immediate aim o this study is to determine the roles of the arterial and cardiopulmonary baroreflexes, and the additional contributions of ventricular dysfunction and orthostatic stress, in determining sympathetic activation and hemodynamic stability during ventricular tachycardia in humans. Design. Using microneurography of the peroneal nerve, sympathetic nerve activity directed to muscle and to skin will be measured and compared in patients with hemodynamically stable and unstable ventricular tachycardia. A series of interventions which selectively activate arterial and cardiopulmonary baroreceptors will be performed

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to determine the contribution of each to sympathetic responses observed during induced ventricular tachycardia or rapid ventricular pacing. Patients with a wide range of ventricular function will be studied, including those with advanced heart failure and patients who have undergone orthotopic heart transplant (which denervates cardiopulmonary baroreceptors). Chaos theory will be used to analyze sympathetic recordings in the different patient groups, based on preliminary results suggesting qualitative differences between normal subjects and heart failure patients. Significance. The knowledge gained from these studies may serve as a basis for the development of medical and surgical therapies directed at the correction of the underlying abnormalities that predispose the patient to hemodynamically unstable ventricular tachycardia degenerating into ventricular fibrillation and sudden cardiovascular death. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SYSTOLIC CARDIAC FUNCTION IN OBESITY AND EXERCISE Principal Investigator & Institution: Carroll, Joan F.; Integrative Physiology; University of North Texas Hlth Sci Ctr Fort Worth, Tx 761072699 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted from applicant's abstract) The candidate's immediate career goals are to study the role of the beta-receptor signaling pathway in mediating systolic dysfunction in obesity, and the role of exercise training in attenuating obesity-related cardiovascular defects. The Department of Integrative Physiology at the University of North Texas Health Science Center is uniquely suited to help the candidate achieve these goals. Within the department, there is a wide variety of expertise in human, animal, in vivo, and in vitro studies in cardiovascular physiology and endocrinology. This will aid in developing expertise with a variety of surgical, laboratory, and assay techniques to study cardiac function. Further, the Cardiovascular Research Institute at the University of North Texas Health Science Center provides access to research efforts of molecular biologists, pharmacologists, physiologists and physicians from within the institution and from nearby institutions. This will benefit career development by providing opportunities to integrate knowledge from many fields which impact cardiovascular research. The current proposal has three major goals: 1) to determine mechanisms associated with reduced cardiac contractile responsiveness to betaadrenergic stimulation in obesity, 2) to determine the role of exercise training in attenuation of obesity-induced abnormalities in cardiac function, and 3) to determine the role of obesity, separate from hypertension, in contributing to systolic dysfunction in sedentary and trained animals. The investigators hypothesize that there are multiples sites of decreased activity in the beta- signaling pathway in obesity. Thus, they will use the rabbit method of dietary-induced obesity to compare function of lean animals with that of obese animals after 12 weeks of a high fat diet. They will use the Langendorff isolated heart preparation and appropriate assay and western blotting techniques to analyze the role of the beta-receptor and four sites of post- receptor activity in contributing to cardiac abnormalities in obesity. The investigators also hypothesize that exercise training during the development of obesity will attenuate or prevent obesityrelated cardiovascular abnormalities. They will determine whether exercise training will 1) reduce obesity-related hypertension, resting tachycardia, and neurohumoral activation, and 2)attenuate obesity-related decreases in responsiveness to betaadrenergic stimulation. They will examine hemodynamics and neurohumoral activation in vivo and use the isolated heart preparation to determine the role of exercise training in increasing responsiveness to beta-adrenergic stimulation. Finally, they hypothesize that obesity has an independent effect on cardiac hypertrophy and systolic dysfunction.

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They will test this hypothesis by maintaining blood pressure at control levels as obesity develops before testing for responsiveness to beta-adrenergic stimulation. Insight into mechanisms whereby obesity increases risk for congestive heart failure may lead to advances in therapeutic modalities for prevention and treatment of heart failure in obese patients. Information on mechanisms whereby exercise training may improve cardiovascular risk profile and cardiac performance in obesity may help reduce risk for development of cardiovascular diseases in obesity. Because such a large segment of the American population is overweight or obese, the knowledge and insight gained from these studies can have far-reaching effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE PATHOPHYSIOLOGY OF T-WAVE ALTERNANS Principal Investigator & Institution: Narayan, Sanjiv M.; Medicine; University of California San Diego La Jolla, Ca 920930934 Timing: Fiscal Year 2002; Project Start 17-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant) This Mentored Patient-Oriented Research Career Development Award application focuses on a program of research designed to study the intracardiac mechanisms underlying T-wave alternans (TWA) of the electrocardiogram in individuals with prior myocardial infarcts and depressed cardiac systolic function in order to improve its computation and therefore its ability to predict those who are at risk for ventricular tachycardia (VT) or fibrillation (VF). This work will build on the applicant?s prior research and training in clinical cardiology and invasive electro-physiology, as well as in basic science, computer science and numerical methods. The proposed research will test the hypothesis that programmed ventricular stimulation in patients with ischemic heart disease and left ventricular dysfunction induces proarrhythmic nonuniformities in ventricular repolarization, and results in redistribution of TWA late in the T-wave, and TWA phase reversal, that are detectable by novel analyses of the ECG. There are two specific aims: 1) To establish that an increased magnitude of TWA late in the T-wave and TWA phase reversal parallel changes in the endocardial dispersion of ventricular repolarization measured, using monophasic action potentials, during progressive programmed ventricular stimulation leading to the induction of VT/VF. 2) To prospectively test, in patients with ischemic heart disease and left ventricular dysfunction, the performance of a new index of myocardial electrical instability, derived from the data calibrating TWA late magnitude and phase to the dispersion of monophasic action potential duration obtained in the research performed to fulfill Specific Aim 1, in predicting the incidence of spontaneous VT/VF. The applicant will perform this work under the supervision and guidance of his Mentor, and with guidance from a Scientific Advisory Committee comprising experts in basic and clinical electrophysiology, in the interpretation of monophasic action potentials, in numeric modeling and signal processing, in statistics and in clinical research. This structured approach will ensure the successful completion of this project and, in this way, the development of the applicant into an independent clinicianinvestigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THREE DIMENSIONAL VORTEX LIKE REENTRY IN CORONARY PERFUSED VENTRICULAR WALL Principal Investigator & Institution: Pertsov, Arkady M.; Associate Professor; Upstate Medical University Research Administration Syracuse, Ny 13210

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Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2003 Summary: The electrophysiological mechanisms of polymorphic ventricular tachycardia and fibrillation remain poorly understood. The surface manifestations as well as limited three-dimensional (3D) information obtained using arrhythmias. In the proposed study, we will utilize a new experimental method (transillumination) that should significantly enhance our ability to study 3D reentrant activity via visualization of its organizing center-filament. Using transillumination in combination with conventional optical mapping we will test the following major hypotheses: 1. In 3D ventricular myocardium, the filament tends to align parallel to myocardial fibers. 3. Sustained polymorphic ventricular tachycardia and fibrillation are maintained by stable filaments concealed in the depth of myocardial wall. Hypotheses 1 and 2 are based on preliminary computer simulations of 3D myocardial wall with realistic fiber geometry. Hypotheses 3 is supported by electrically induced tachycardia or fibrillation. The specific aims of our study are as follows: 1. To identify the mechanisms controlling spatial orientation and dynamics of the filament in computer models of ventricular wall with realistic fiber organization. 2. To study the evolution of the scroll-wave filament during sustained and non-sustained arrhythmias in isolated coronary-perfused preparations of sheep right and left ventricles using a transillumination technique. 3. To determine the role of stable filaments in the maintenance in the maintenance mechanisms of complex reentrant ventricular arrhythmias. The ultimate goal of this study is to assess the possibility of terminating those arrhythmias by controlling the evolution of the scroll wave filament. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TOWARDS FIBRILLATION

A

NON-INVASIVE

THERAPY

FOR

ATRIAL

Principal Investigator & Institution: Scherlag, Benjamin J.; Medicine; University of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 73126 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-MAR-2005 Summary: (provided by applicant): Atrial fibrillation (AF) has been called the arrhythmia of the 21st century since it is the most common arrhythmia whose prevalence increases as the population ages. Recent clinical studies have suggested that trains of rapid electrical discharges from the pulmonary veins induce paroxysmal (P) or episodic AF. The mechanism by which this focal activity leads to PAF is unknown. Therefore, our initial studies have concentrated on this mechanism providing for a 4 step strategy towards developing a non-invasive therapy for PAF 1) Demonstration that local autonomic nerve stimulation at the base of the pulmonary veins can cause the conversion of rapid focal firing from the pulmonary veins into PAF. 2) Demonstration that low level electrical stimuli applied to the vagosympathetic trunks can condition the cardiac ganglia so that stimuli applied to the latter will manifest a significant alteration in the threshold for induction of PAF. 3) Utilize time varying electromagnetic fields (EMFs) applied to the cervical vagosympathetic trunks in order to significantly alter the AF threshold. 4) Since magnetic components of EMFs penetrate soft tissues and bone unattenuated, our final approach will employ a large 18" Helmholtz coil by which the EMF will be applied across the chest to induce low-level electrical stimulation of intrinsic cardiac nerves. Again, the objective is to demonstrate electrical conditioning of the local cardiac autonomic nerves in order to alter baseline conditions for AF induction. In this developmental phase, all of these studies will be acutely performed in Napentobarbital anesthetized dogs. Our long-term objectives relate to the extension of the previously described strategies to animal models of chronic or sustained AF which if applied to the clinical arena would profoundly alter the treatment of these arrhythmias

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in man. This new therapeutic approach could be utilized as a non-invasive application or incorporated into an implantable device for treatment of patients with PAF. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TREATMENT OF ORTHOSTATIC TACHYCARDIA Principal Investigator & Institution: Robertson, David H.; Professor of Medicine, Pharmacology And; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-DEC-2001; Project End 30-NOV-2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: T-TUBULES AND L-TYPE CALCIUM CHANNELS IN HEART FAILURE Principal Investigator & Institution: Kamp, Timothy J.; Assistant Professor; Medicine; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 01-JUL-1999; Project End 31-MAY-2004 Summary: (adapted from the applicant's description): Congestive heart failure results in substantial structural and functional changes at the level of cardiac myocytes. Preliminary results indicate that the t-tubular network is severely depleted or absent in failing canine and human myocytes. This observation has important functional consequences for excitation-contraction (E-C) coupling (which requires close opposition between surface membrane L-type Ca channels (DHPRs) in the t-tubule membrane and Ca release channels (RyRs) in the SR) and beta-adrenergic signal transduction. The general hypothesis of the proposed research is that sub-cellular remodeling of the ttubule system and junctional domains results in contractile failure and abnormal betaadrenergic regulation in failing ventricular myocytes. This general hypothesis will be tested in myocytes obtained from a tachycardia pacing-induced dog model and confirmed on human cells obtained from patients undergoing cardiac transplantation. The 5 specific aims of the proposed research are: 1) characterization of the t-tubule system density in failing and control hearts using 2-photon and confocal microscopy, 2) quantification of DHPRs in failing and control hearts using electrophysiological and biochemical techniques, 3) define the mechanism of uncoupling of the DHPR and RyR in failing myocytes, 4) determine the mechanism of uncoupling of beta-adrenergic receptors and DHPRs, and 5) perform confocal immunolocalization studies of DHPR subunits, RyR, beta-adrenergic receptors and G-proteins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: UTILIZING ETHYL NITRATE GAS IN LAPAROSCOPIC SURGERY Principal Investigator & Institution: Reynolds, James D.; Anesthesiology; Duke University Durham, Nc 27706 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2007 Summary: The principal goal of this project is to evaluate the ability of ethyl nitrate to attenuate the reduced tissue perfusion and respiratory acidosis produced during carbon dioxide pneumoperitoneum. The studies will use a novel method of drug delivery: inclusion of ethyl nitrate in the insufflating gas. Laparoseopy has rapidly become the method of choice for surgical intervention to correct abdominal pathologies. However, pneumoperiteneum, the act of insufflating the peritoneal cavity with gas, is not without physiologic consequence: pulmonary function is impaired and organ blood flows

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altered. In addition, due to its plasma solubility, insufflation with CO2 will increase pCOz and decrease blood pH, actions that can produce respiratory acidosis, tachycardia, and arrhythmia. The overall effects can become profound in the presence of underlying vascular disease, in[ the elderly, if the patient is pregnant, and/or when the duration of surgery is extended. In all situations, tissue ischemia and fetal ischemia (where applicable) can produce significant morbidity. To control this, it is a logical supposition that administration of a vasoactive agent to increase tissue blood flow and gas exchange would be beneficial. For the purposes of this study, we propose to introduce a nitric oxide donator (ethyl nitrate; E-NO) into the insufflating gas. As the released nitric oxide can act locally (i.e. within the peritoneum) as well as entering the systemic circulation and, in the case of the gravid patient, the fetal circulation (either by diffusion or maternal-fetal exchange), this would appear to be an ideal methodology to abate the CO2 pnenmoperiteneum-mediated changes in physiologic status. Such abatement is expected to be of long-term benefit to all laparoscopic patients including the parturient and her fetus. To evaluate this novel therapy, we will test two research hypotheses: 1. In the non-gravida, inclusion of E-NO in the insufflating gas attenuates the tissue perfusion changes produced by CO2 pneumoperitoneum; and 2. In the parturient, inclusion of E-NO during maternal pneumoperitoneum stabilizes fetal physiologic status. Studies will utilize adult swine and pregnant sheep. Completion of this investigation will produce clinically-relevant information that will be of significant interest to surgeons With patients in need of laparoscopic surgery and to obstetricians who are presented with parturients in abdominal distress. It is expected that the results of these studies will be used to further develop and refine standards of care for human laparoscopy and will lead to a novel therapy for controlling the blood flow changes produced during pneumoperitoneum. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VIDEO INITIATION/TERMINATION

IMAGING

OF

CARDIAC

REENTRY

Principal Investigator & Institution: Gray, Richard A.; Biomedical Engineering; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: Sudden cardiac death is the leading cause of fatalities in the industrialized world. Ventricular fibrillation (VF) is the underlying cause of the majority of these deaths. The only effective means to save the lives of these individuals is to apply high energy electric fields from widely spaced electrodes to terminate VF. These high energy "shocks" can also induce VF, if they are applied during the "vulnerable period" of normal sinus or pace rhythms. The outcome following a shock is determined largely by the charges in transmembrane potential (Vm) during the shock. However, very little is known about the shock- induced changes in Vm in the whole heart and how they relate to the events following a shock. It is thought that the changes in Vm during applied electric fields is a nonlinear function of: 1) the Vm pattern immediately before the sock; 2) the strength and time course (waveform) of the electric field; and 3) the dynamic response of cardiac cells to stimuli. We hypothesize that: I Electric fields greater than some critical strength prevent wave front propagation throughout the heart, and if these shocks are sufficiently long in duration, a steady state pattern of Vm will be established. Vm at the end of short duration shocks, for a constant electric field above this critical strength, can be predicted from Vm at the beginning of the shock and the steady state Vm pattern achieved during long duration shocks. II) The nonlinear response of cardiac cells, most importantly all-or-none depolarization and repolarization, plays an

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important role in the generation of new wave fronts at the end of the shock which may lead to reentry. III) The spatial pattern of Vm at the end of the shock can be related to reentry formation and hence the outcome resulting from the shock. In particular, spatial patterns of cardiac phase can be formally related to reentry via phase singularities and reentry will only occur following a shock if a phase singularity exists at the end of the shock. Our overall goal is to provide the first precise understanding of the factors that determine the changes in Vm during a shock and how the pattern of Vm at the end of the applied electric field affects the outcome of the shock. This goal will be achieved by: 1) recording Vm from the surface of the heart during and following electric shocks given during pacing, monomorphic tachycardia, and fibrillation; 2) recording them response to stimuli in isolated ventricular myocytes; and 3) relating the patterns of membrane potential at the end of shocks to outcome. Furthermore, changes in Vm in single cells and patterns of Vm from the heart surface will be analyzed in terms of a cardiac phase variable which provides a mathematical framework for the examination of cellular dynamics and reentrant waves. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VIRTUAL ELECTRICAL-ANATOMICAL IMAGING OF THE HEART Principal Investigator & Institution: Khoury, Dirar Shafiq.; Assistant Professor; Medicine; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-JAN-2002; Project End 31-DEC-2005 Summary: (Provided by Applicant): Atrial fibrillation (AF) is the most common heart rhythm disorder: it affects more than two million Americans, is responsible for one-third of all strokes over the age of 65 years, and annually costs 9 billion dollars to manage. Furthermore, about 300,000 Americans die of sudden cardiac death annually, primarily due to ventricular rhythm disorders (ventricular tachycardia (VT and fibrillation) which result in intractable, extremely rapid heartbeats. Unfortunately, current pharmacological therapy for managing these disorders is often ineffective, thereby shifting emphasis to nonpharmacological therapy (e.g. ablation and pacing). Catheter ablation has been successful in managing many atrial and a few ventricular rhythm disorders. However, due to limitations in present mapping techniques, brief, chaotic, or complex rhythms such as AF and VT cannot be mapped adequately, resulting in their unsuccessful elimination. Advancing the management of abnormal heartbeats is contingent on developing mapping techniques that identify their mechanisms, localize their sites of origin, and elucidate effects of therapy. Our objective is to develop a catheter-based, cardiac electrophysiological imaging technique that simultaneously maps multiple endocardial electrograms on a beat-by-beat basis and combines three-dimensional activation-recovery sequences with endocardial anatomy. The hypothesis is that virtual electrical-anatomical imaging of the heart based on (1) cavitary electrograms that are measured with a noncontact, multielectorde probe and (2) three-dimensional endocardial anatomy that is determined with integrated, intracardiac echocardiography (ICE), provides an effective and efficient means to diagnose abnormal heartbeats and deliver therapy. Therefore, we will: (1) build a noncontact, electrical-anatomical imaging catheter-system that carries both a multielectrode catheter-probe for acquiring cavitary electrograms from multiple directions, and a central ICE catheter for acquiring endocardial anatomical images; (2) advance novel mathematical methods to compute endocardial electrograms and reconstruct three-dimensional activation-recovery sequences based on noncontact cavitary probe electrograms and geometry determined by ICE; and, (3) prove the utility of virtual electrical-anatomical imaging in the canine beating heart by characterizing models of AF, myocardial infarction, and VT and

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identifying their components, and by quantifying ablation lesions as assessed by both electrical and echocardiographic criteria. The proposed catheter can be introduced into the blood-filled cavity without surgery and provides three-dimensional electricalanatomical images on a beat-by-beat basis. With this approach, one can pinpoint the site of origin and type of abnormal heartbeats and advance their therapy. In line with a Bioengineering Research Grant, the research develops a system the outcome of which is to improve the benefit-risk and benefit-cost relationships of patient care and advance heart rhythm-related research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “tachycardia” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for tachycardia in the PubMed Central database: •

ABLATIVE TECHNIQUES FOR SURGICAL TREATMENT OF PAROXYSMAL TACHYCARDIA. by Cooley DA, Ott DA, Gillette PC, Garson A Jr.; 1979 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=287815

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Active Lymphocytic Myocarditis Treated with Murine OKT3 Monoclonal Antibody in a Patient Presenting with Intractable Ventricular Tachycardia. by Bilinska ZT, Grzybowski J, Szajewski T, Stepinska J, Michalak E, Walczak E, Wagner T, Kwiatkowska B, Ruzyllo W.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=116737

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Amiodarone for control of recurrent ventricular tachycardia secondary to cardiac metastasis. by Leak D.; 1998; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=325549

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Assessment and Treatment of Tachycardias in Ischemic Heart Disease. by Fontaine G.; 1982 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=351675

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Assessment of Tachycardia in Preexcitation Syndromes. by Gallagher JJ, Orgain ES.; 1982 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=351673

3 4

Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.

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•

Assessment of Tachycardia-Prone Individuals. by Wellens HJ.; 1982 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=351672

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Cardiac Sarcoidosis: Two Cases with Ventricular Tachycardia and Review of Cardiac Involvement in Sarcoid. by Wilkins CE, Barron T, Lowrimore MG, Massumkhani GA, Klima T, Younis AC, Treistman B, Hall RJ.; 1985 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=341894

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Cardiac Sarcoidosis: Two Cases With Ventricular Tachycardia and Review of Cardiac Involvement in Sarcoid. by Lam CR.; 1986 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=324640

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Catheter Ablation Techniques in Patients with Supraventricular Tachycardia. by Scheinman MM.; 1986 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=324673

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Cryoablation of Incessant Ventricular Tachycardia: Case Report and Long-Term Follow-Up. by Afshar H, Rasekh A, Treistman B, Leeuwen CV, Duncan JM, Massumi A.; 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101020

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Cryosurgical Modification of the Atrioventricular Node for Treatment of Atrioventricular Junctional Reentrant Tachycardia. by Perin EC, Petersen F, RizoPatron C, Ott DA, Massumi A.; 1991; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=324964

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Difference in end-tidal CO2 between asphyxia cardiac arrest and ventricular fibrillation/pulseless ventricular tachycardia cardiac arrest in the prehospital setting. by Grmec S, Lah K, Tusek-Bunc K.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=374361

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Electrophysiologic characteristics of sudden QRS axis deviation during orthodromic tachycardia. Role of functional fascicular block in localization of accessory pathway. by Jazayeri MR, Caceres J, Tchou P, Mahmud R, Denker S, Akhtar M.; 1989 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=303771

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Electrophysiologic Testing: Predictive of Amiodarone Efficacy in Recurrent Sustained Ventricular Tachycardia? by Mas IJ, Massumi A, Harlan M, Seger JJ, Hall RJ.; 1987 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=324762

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Exercise-Induced Right Ventricular Tachycardia and Arrhythmogenic Right Ventricular Dysplasia: Electrophysiologic and Therapeutic Considerations. by Solomon SL, Van Osdol KD, Massumi A, Warda M, Hall RJ.; 1983 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=344364

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Increased Sympathetic Nervous System Activity as Cause of Exercise-Induced Ventricular Tachycardia in Patients with Normal Coronary Arteries. by Ozdemir O, Soylu M, Demir AD, Topaloglu S, Alyan O, Geyik B, Kutuk E.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161893

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Neonatal presentation of ventricular tachycardia and a Reye-like syndrome episode associated with disturbed mitochondrial energy metabolism. by Scaglia F, Scheuerle AE, Towbin JA, Armstrong DL, Sweetman L, Wong LJ.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=140035

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Prevention of AV Nodal Reentry Tachycardia by Oral Amiodarone: An Alternative Mechanism of Action. by Gold RL, Haffajee CI, Entes KL.; 1987 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=324700

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Programmed electrical stimulation and Amiodarone therapy for the control of persistent junctional tachycardia. by Critelli G, Adinolfi L, Perticone F, Condorelli M.; 1981 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=287922

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Rapid Ventricular Tachycardias Associated with Cilostazol Use. by Gamssari F, Mahmood H, Ho JS, Villareal RP, Liu B, Rasekh A, Garcia E, Massumi A.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=116744

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Role of Retrograde His Purkinje Block in the Initiation of Supraventricular Tachycardia by Ventricular Premature Stimulation in the Wolff-Parkinson-White Syndrome. by Akhtar M, Shenasa M, Schmidt DH.; 1981 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=370663

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Role of Tachycardia as an Inotropic Stimulus in Man. by Ricci DR, Orlick AE, Alderman EL, Ingels NB Jr, Daughters GT II, Kusnick CA, Reitz BA, Stinson EB.; 1979 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=372004

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Sinus versus nonsinus tachycardia in the emergency department: Importance of age and heart rate. by Pinto DS, Ho KK, Zimetbaum PJ, Pedan A, Goldberger AL.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=184452

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Slowed conduction and ventricular tachycardia after targeted disruption of the cardiac sodium channel gene Scn5a. by Papadatos GA, Wallerstein PM, Head CE, Ratcliff R, Brady PA, Benndorf K, Saumarez RC, Trezise AE, Huang CL, Vandenberg JI, Colledge WH, Grace AA.; 2002 Apr 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122928

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Surgical Treatment of Tachycardias in Preexcitation Syndromes. by Sealy WC.; 1982 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=351660

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Surgical Treatment of Tachycardias in Preexcitation Syndromes. by Sealy WC.; 1982 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=351676

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Tachycardia associated with moxifloxacin. by Siepmann M, Kirch W.; 2001 Jan 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26602

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Transesophageal electrocardiography and adenosine in the diagnosis of wide complex tachycardia. by Lopez JA, Lufschanowski R, Massumi A.; 1994; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=325147

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Treatment of Resistant Ventricular Tachycardia with Endocavitary Fulguration and Antiarrhythmic Therapy, Compared to Antiarrhythmic Therapy Alone: Experience in 111 Consecutive Cases with a Mean Follow-up of 18 Months. by Fontaine G, Frank R, Tonet JL, Gallais Y, Touzet I, Todorova M, Baraka M, Grosgogeat Y.; 1986 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=324671

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Ventricular tachycardia during repair of gastroschisis. by Saidi AS, Friedman RA, el Said H, Nuchtern JG, Fenrich AL.; 1998; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=325578

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with tachycardia, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “tachycardia” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for tachycardia (hyperlinks lead to article summaries): •

A Long RP' Interval Tachycardia: what is the mechanism? Author(s): Intini A, Stambler B, Varma N. Source: Journal of Cardiovascular Electrophysiology. 2003 December; 14(12): 1379-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14678118

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A missense mutation in a highly conserved region of CASQ2 is associated with autosomal recessive catecholamine-induced polymorphic ventricular tachycardia in Bedouin families from Israel. Author(s): Eldar M, Pras E, Lahat H. Source: Cold Spring Harb Symp Quant Biol. 2002; 67: 333-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12858557

6

PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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A narrow QRS complex tachycardia: what is the mechanism? Author(s): Okumura Y, Watanabe I, Kofune T, Takagi Y, Saito S, Ozawa Y, Kanmatsuse K. Source: Pacing and Clinical Electrophysiology : Pace. 2003 September; 26(9): 1897-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12930506

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A narrow-QRS tachycardia: what is the mechanism? Author(s): Vijayaraman P, Kok LC, Ellenbogen KA. Source: Journal of Cardiovascular Electrophysiology. 2003 June; 14(6): 670-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12875432

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A not-so-narrow complex tachycardia. Author(s): Indik JH. Source: Cardiology in Review. 2003 September-October; 11(5): 247-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12943599

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A novel form of familial bidirectional ventricular tachycardia. Author(s): Nof E, Lahat H, Constantini N, Luria D, Rosenfeld G, Eldar M, Pras E, Glikson M. Source: The American Journal of Cardiology. 2004 January 15; 93(2): 231-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14715357

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A wide QRS tachycardia inducible only by atrial pacing and terminable only by ventricular pacing. Author(s): Li H, Rovang K, Hee T. Source: Pacing and Clinical Electrophysiology : Pace. 2003 November; 26(11): 2170-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14622321

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Ablation of epicardial macroreentrant ventricular tachycardia associated with idiopathic nonischemic dilated cardiomyopathy by a percutaneous transthoracic approach. Author(s): Swarup V, Morton JB, Arruda M, Wilber DJ. Source: Journal of Cardiovascular Electrophysiology. 2002 November; 13(11): 1164-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12475110

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Ablation of postinfarction ventricular tachycardia guided by isolated diastolic potentials. Author(s): Strohmer B, Hwang C. Source: Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology. 2003 October; 5(4): 375-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14753635

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Acute blood pressure effects at the onset of supraventricular and ventricular tachycardia. Author(s): Taneja T, Kadish AH, Parker MA, Goldberger JJ. Source: The American Journal of Cardiology. 2002 December 15; 90(12): 1294-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12480037

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Acute results of transvenous cryoablation of supraventricular tachycardia (atrial fibrillation, atrial flutter, Wolff-Parkinson-White syndrome, atrioventricular nodal reentry tachycardia). Author(s): Rodriguez LM, Geller JC, Tse HF, Timmermans C, Reek S, Lee KL, Ayers GM, Lau CP, Klein HU, Crijns HJ. Source: Journal of Cardiovascular Electrophysiology. 2002 November; 13(11): 1082-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12475096

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Advances in ablation therapy for complex arrhythmias: atrial fibrillation and ventricular tachycardia. Author(s): Lin D, Marchlinski FE. Source: Current Cardiology Reports. 2003 September; 5(5): 407-14. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12917057

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Amiodarone therapy for drug-refractory fetal tachycardia. Author(s): Strasburger JF, Cuneo BF, Michon MM, Gotteiner NL, Deal BJ, McGregor SN, Oudijk MA, Meijboom EJ, Feinkind L, Hussey M, Parilla BV. Source: Circulation. 2004 January 27; 109(3): 375-9. Epub 2004 Jan 19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14732753

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An 82-year-old man with an implantation of a CPI Ventak AV II DR device for sustained ventricular tachycardia. Author(s): Marieb MA, Schwartz KV. Source: Pacing and Clinical Electrophysiology : Pace. 2003 November; 26(11): 2209. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14622330

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An unusual cause of tachycardia. Author(s): Klafkowski G, Newall N, Sampson C. Source: The British Journal of Radiology. 2003 June; 76(906): 427-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12814932

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Anterograde slow pathway is not the same as retrograde slow pathway conducted in the reverse direction in patients with uncommon atrioventricular nodal reentrant tachycardia. Author(s): Ooie T, Tsuchiya T, Ashikaga K, Honda T, Takahashi N. Source: Journal of Cardiovascular Electrophysiology. 2003 July; 14(7): 722-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12930252

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71

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Area ablation of ventricular tachycardia in a patient with arrhythmogenic right ventricular cardiomyopathy. Author(s): de Groot NM, Schalij MJ, van der Wall EE. Source: Heart (British Cardiac Society). 2003 July; 89(7): 703. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12807832

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Atrioventricular block during atrioventricular nodal reentrant tachycardia is not always benign. Author(s): Tokano T, Nakata Y, Sasaki A, Mineda Y, Sumiyoshi M, Nakazato Y, Daida H. Source: Japanese Heart Journal. 2003 September; 44(5): 789-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14587661

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Atrioventricular nodal reentry tachycardia with multiple AH jumps: electrophysiological characteristics and radiofrequency ablation. Author(s): Kuo CT, Luqman N, Lin KH, Cheng NJ, Hsu TS, Lee YS. Source: Pacing and Clinical Electrophysiology : Pace. 2003 September; 26(9): 1849-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12930499

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Automatic discrimination between supraventricular and ventricular tachycardia using a multilayer perceptron in implantable cardioverter defibrillators. Author(s): Rojo-Alvarez JL, Garcia-Alberola A, Arenal-Maiz A, Pineiro-Ave J, ValdesChavarri M, Artes-Rodriguez A. Source: Pacing and Clinical Electrophysiology : Pace. 2002 November; 25(11): 1599-604. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12494618

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Baseline reconstruction for localization of rapid ventricular tachycardia from body surface potential maps. Author(s): Jokiniemi T, Simelius K, Nenonen J, Tierala I, Toivonen L, Katilal T. Source: Physiological Measurement. 2003 August; 24(3): 641-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14509302

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Becker muscular dystrophy with bundle branch reentry ventricular tachycardia. Author(s): Negri SM, Cowan MD. Source: Journal of Cardiovascular Electrophysiology. 1998 June; 9(6): 652-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9654233

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Benefit of pacing and beta-blockers in idiopathic repetitive polymorphic ventricular tachycardia. Author(s): Perez-Castellano N, Rodriguez JC, Medina O, Nieto V. Source: Journal of Cardiovascular Electrophysiology. 2001 November; 12(11): 1304-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11761421

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Best approach to nonsustained ventricular tachycardia? Author(s): Tak T. Source: Postgraduate Medicine. 2002 November; 112(5): 99. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12462189

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Bidirectional tachycardia eliminated with radiofrequency ablation. Author(s): Li JM, Welch PJ, Zagrodzky JD, Hamdan MH. Source: Pacing and Clinical Electrophysiology : Pace. 2002 December; 25(12): 1786-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12520685

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Bidirectional tachycardia: two cases and a review. Author(s): Al-Khafaji A, Corwin HL, Adhar GC, Greenberg ML. Source: Anesthesia and Analgesia. 2002 August; 95(2): 310-5, Table of Contents. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12145041

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Bidirectional ventricular tachycardia after radiofrequency ablation of idiopathic left ventricular tachycardia. Author(s): Kuo JY, Tai CT, Lin YK, Yu WC, Chen SA. Source: Pacing and Clinical Electrophysiology : Pace. 2001 September; 24(9 Pt 1): 1412-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11584465

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Bidirectional ventricular tachycardia and channelopathy. Author(s): Laohakunakorn P, Benson DW, Yang P, Yang T, Roden DM, Kugler JD. Source: The American Journal of Cardiology. 2003 October 15; 92(8): 991-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14556882

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Bidirectional ventricular tachycardia. Author(s): Ito S, Tada H, Naito S, Taniguchi K. Source: Journal of Cardiovascular Electrophysiology. 2002 December; 13(12): 1312. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12521355

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Biventricular implantable cardioverter defibrillator use in a patient with heart failure and ventricular tachycardia secondary to Emery-Dreifuss syndrome. Author(s): Walker S, Levy T, Rex S, Paul VE. Source: Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology. 1999 July; 1(3): 206-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11225801

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Blunt cardiac injury presenting as unsuspected ventricular tachycardia. Author(s): Vogler A, Seaberg DC. Source: The American Journal of Emergency Medicine. 2001 November; 19(7): 607-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11699018

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Broad complex tachycardia--Part I. Author(s): Edhouse J, Morris F. Source: Bmj (Clinical Research Ed.). 2002 March 23; 324(7339): 719-22. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11909791

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Brugada syndrome with monomorphic ventricular tachycardia in a one-year-old child. Author(s): Sastry BK, Narasimhan C, Soma Raju B. Source: Indian Heart J. 2001 March-April; 53(2): 203-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11428478

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Brugada syndrome with ventricular tachycardia and fibrillation related to hypokalemia. Author(s): Araki T, Konno T, Itoh H, Ino H, Shimizu M. Source: Circulation Journal : Official Journal of the Japanese Circulation Society. 2003 January; 67(1): 93-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12520160

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Brugada syndrome: a case report of monomorphic ventricular tachycardia. Author(s): Boersma LV, Jaarsma W, Jessurun ER, Van Hemel NH, Wever EF. Source: Pacing and Clinical Electrophysiology : Pace. 2001 January; 24(1): 112-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11227955

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Brugada-type ECG with polymorphic ventricular tachycardia: a red herring for isolated right ventricular infarction. Author(s): Hsu LF, Ding ZP, Kam R, Teo WS, Lim YL. Source: International Journal of Cardiology. 2003 October; 91(2-3): 255-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14559142

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Bundle branch reentrant tachycardia in patients with apparent normal His-Purkinje conduction: the role of functional conduction impairment. Author(s): Li YG, Gronefeld G, Israel C, Bogun F, Hohnloser SH. Source: Journal of Cardiovascular Electrophysiology. 2002 December; 13(12): 1233-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12521339

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Bundle branch re-entrant ventricular tachycardia in a patient with structurally normal heart. Author(s): Gupta AK, Vajifdar BU, Vora AM. Source: Indian Heart J. 1999 January-February; 51(1): 80-2. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10327786

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Bundle branch reentrant ventricular tachycardia in a patient with the Brugada electrocardiographic pattern. Author(s): Mazur A, Iakobishvili Z, Kusniec J, Strasberg B. Source: Annals of Noninvasive Electrocardiology : the Official Journal of the International Society for Holter and Noninvasive Electrocardiology, Inc. 2003 October; 8(4): 352-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14516293

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Bystander cavo-tricuspid isthmus activation during post-incisional intra-atrial reentrant tachycardia. Author(s): Tritto M, De PR, Zardini M, Spadacini G, Salerno-Uriarte JA. Source: Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology. 2002 January; 4(1): 91-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11846322

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Cardiology patient pages. Supraventricular tachycardia. Author(s): Wang PJ, Estes NA 3rd. Source: Circulation. 2002 December 17; 106(25): E206-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12485968

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Cardiovascular magnetic resonance of iatrogenic ventricular scarring due to catheter ablation for left ventricular tachycardia. Author(s): Sievers B, Brandts B, Moon JC, Pennell DJ, Trappe HJ. Source: International Journal of Cardiology. 2003 October; 91(2-3): 249-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14559140

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Case reports and review of Postural Orthostatic Tachycardia syndrome (POTS). Author(s): Carothers B, Schmidt L, Puri V. Source: J Ky Med Assoc. 2003 December; 101(12): 549-52. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14689686

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Cases from the Osler Medical Service at Johns Hopkins University. Digitalis toxicity with bidirectional ventricular tachycardia. Author(s): Piccini J, Zaas A. Source: The American Journal of Medicine. 2003 July; 115(1): 70-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12867240

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Catecholaminergic polymorphic ventricular tachycardia: electrocardiographic characteristics and optimal therapeutic strategies to prevent sudden death. Author(s): Sumitomo N, Harada K, Nagashima M, Yasuda T, Nakamura Y, Aragaki Y, Saito A, Kurosaki K, Jouo K, Koujiro M, Konishi S, Matsuoka S, Oono T, Hayakawa S, Miura M, Ushinohama H, Shibata T, Niimura I. Source: Heart (British Cardiac Society). 2003 January; 89(1): 66-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12482795

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Catheter ablation of sinoatrial re-entry tachycardia in a 2 month old infant. Author(s): Simmers T, Sreeram N, Wittkampf F. Source: Heart (British Cardiac Society). 2003 January; 89(1): E1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12482811

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Catheter ablation of subepicardial ventricular tachycardia using electroanatomic mapping. Author(s): Ouyang F, Bansch D, Schaumann A, Ernst S, Linder C, Falk P, Hachiya H, Kuck KH, Antz M. Source: Herz. 2003 November; 28(7): 591-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14689119

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Catheter ablation of supraventricular tachycardia in the transplanted heart: a case series and literature review. Author(s): Magnano AR, Garan H. Source: Pacing and Clinical Electrophysiology : Pace. 2003 September; 26(9): 1878-86. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12930504

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Catheter ablation of ventricular tachycardia in patients with ischemic heart disease. Author(s): Soejima K, Stevenson WG. Source: Current Cardiology Reports. 2003 September; 5(5): 364-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12917050

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Catheter ablation of ventricular tachycardia in remote myocardial infarction: substrate description guiding placement of individual linear lesions targeting noninducibility. Author(s): Kottkamp H, Wetzel U, Schirdewahn P, Dorszewski A, Gerds-Li JH, Carbucicchio C, Kobza R, Hindricks G. Source: Journal of Cardiovascular Electrophysiology. 2003 July; 14(7): 675-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12930243

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Characterization of endocardial electrophysiological substrate in patients with nonischemic cardiomyopathy and monomorphic ventricular tachycardia. Author(s): Hsia HH, Callans DJ, Marchlinski FE. Source: Circulation. 2003 August 12; 108(6): 704-10. Epub 2003 July 28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12885746

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Chronic inappropriate sinus tachycardia in elderly females. Author(s): Lopera G, Castellanos A, Moleiro F, Huikuri HV, Myerburg RJ. Source: Annals of Noninvasive Electrocardiology : the Official Journal of the International Society for Holter and Noninvasive Electrocardiology, Inc. 2003 April; 8(2): 139-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12848795

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Clinical and electrophysiological characteristics in patients with atrioventricular reentrant and atrioventricular nodal reentrant tachycardia. Author(s): Bottoni N, Tomasi C, Donateo P, Lolli G, Muia N, Croci F, Oddone D, Menozzi C, Brignole M. Source: Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology. 2003 July; 5(3): 225-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12842632

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Clinical course of atrial ectopic tachycardia is age-dependent: results and treatment in children < 3 or > or =3 years of age. Author(s): Salerno JC, Kertesz NJ, Friedman RA, Fenrich AL Jr. Source: Journal of the American College of Cardiology. 2004 February 4; 43(3): 438-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15013128

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Clinical results with catheter ablation: AV junction, atrial fibrillation and ventricular tachycardia. Author(s): Weinstock J, Wang PJ, Homoud MK, Link MS, Estes NA 3rd. Source: Journal of Interventional Cardiac Electrophysiology : an International Journal of Arrhythmias and Pacing. 2003 October; 9(2): 275-88. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14574041

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Clinical usefulness of electrophysiologic testing in patients with ventricular tachycardia and chronic chagasic cardiomyopathy treated with amiodarone or sotalol. Author(s): Leite LR, Fenelon G, Simoes A Jr, Silva GG, Friedman PA, de Paola AA. Source: Journal of Cardiovascular Electrophysiology. 2003 June; 14(6): 567-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12875414

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Coincidence of idiopathic ventricular outflow tract tachycardia and atrioventricular nodal reentrant tachycardia. Author(s): Kautzner J, Cihak R, Vancura V, Bytesnik J. Source: Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology. 2003 July; 5(3): 215-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12842630

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Cor triatriatum with unroofed coronary sinus and persistent left superior vena cava associated with atrial tachycardia. Author(s): Sato T, Suzuki K, Umemura J, Takahashi Y, Tomimoto K. Source: Pediatric Cardiology. 2003 September-October; 24(5): 520-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14627330

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Coronary no-flow and ventricular tachycardia associated with habitual marijuana use. Author(s): Rezkalla SH, Sharma P, Kloner RA. Source: Annals of Emergency Medicine. 2003 September; 42(3): 365-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12944889

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Correlates of functional disability in patients with postural tachycardia syndrome: preliminary cross-sectional findings. Author(s): Benrud-Larson LM, Sandroni P, Haythornthwaite JA, Rummans TA, Low PA. Source: Health Psychology : Official Journal of the Division of Health Psychology, American Psychological Association. 2003 November; 22(6): 643-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14640863

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Decreased skeletal muscle pump activity in patients with postural tachycardia syndrome and low peripheral blood flow. Author(s): Stewart JM, Medow MS, Montgomery LD, McLeod K. Source: American Journal of Physiology. Heart and Circulatory Physiology. 2004 March; 286(3): H1216-22. Epub 2003 October 23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14576081

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Definition of the reentry circuit with demonstration of a low frequency diastolic potential in a patient with verapamil-sensitive idiopathic left ventricular tachycardia. Author(s): Wen MS, Yeh SJ, Wu D. Source: Journal of Electrocardiology. 2002 October; 35(4): 357-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12395364

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Delineation of intra-atrial reentrant tachycardia circuits after mustard operation for transposition of the great arteries using biatrial electroanatomic mapping and entrainment mapping. Author(s): Zrenner B, Dong J, Schreieck J, Ndrepepa G, Meisner H, Kaemmerer H, Schomig A, Hess J, Schmitt C. Source: Journal of Cardiovascular Electrophysiology. 2003 December; 14(12): 1302-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14678105

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Demonstration of the exact anatomic tachycardia circuit in the fast-slow form of atrioventricular nodal reentrant tachycardia. Author(s): Yamabe H, Shimasaki Y, Honda O, Kimura Y, Hokamura Y. Source: Circulation. 2001 September 11; 104(11): 1268-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11551878

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Demonstration of the exact anatomic tachycardia circuit in the fast-slow form of atrioventricular nodal reentrant tachycardia. Author(s): Patterson E, Scherlag BJ. Source: Circulation. 2002 April 9; 105(14): E80-1; Author Reply E80-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11940558

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Detection of enteroviral RNA (poliovirus types 1 and 3) in endomyocardial biopsies from patients with ventricular tachycardia and survivors of sudden cardiac death. Author(s): Klein RM, Jiang H, Du M, Niederacher D, Picard F, Brehm M, Vester EG, Strauer BE. Source: Scandinavian Journal of Infectious Diseases. 2002; 34(10): 746-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12477325

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Detection of ventricular fibrillation and tachycardia from the surface ECG by a set of parameters acquired from four methods. Author(s): Jekova I, Mitev P. Source: Physiological Measurement. 2002 November; 23(4): 629-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12450264

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Development and validation of an ECG algorithm for identifying the optimal ablation site for idiopathic ventricular outflow tract tachycardia. Author(s): Ito S, Tada H, Naito S, Kurosaki K, Ueda M, Hoshizaki H, Miyamori I, Oshima S, Taniguchi K, Nogami A. Source: Journal of Cardiovascular Electrophysiology. 2003 December; 14(12): 1280-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14678101

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Difference in end-tidal CO2 between asphyxia cardiac arrest and ventricular fibrillation/pulseless ventricular tachycardia cardiac arrest in the prehospital setting. Author(s): Grmec S, Lah K, Tusek-Bunc K. Source: Critical Care (London, England). 2003 December; 7(6): R139-44. Epub 2003 September 24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14624688

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Differences in inducibility and prognosis of in-hospital versus out-of-hospital identified nonsustained ventricular tachycardia in patients with coronary artery disease: clinical and trial design implications. Author(s): Pires LA, Lehmann MH, Buxton AE, Hafley GE, Lee KL; Multicenter Unsustained Tachycardia Trial Investigators. Source: Journal of the American College of Cardiology. 2001 October; 38(4): 1156-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11583897

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Differential effects of adenosine on focal and macroreentrant atrial tachycardia. Author(s): Markowitz SM, Stein KM, Mittal S, Slotwiner DJ, Lerman BB. Source: Journal of Cardiovascular Electrophysiology. 1999 April; 10(4): 489-502. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10355690

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Differential effects of atropine and isoproterenol on inducibility of atrioventricular nodal reentrant tachycardia. Author(s): Stellbrink C, Diem B, Schauerte P, Brehmer K, Schuett H, Hanrath P. Source: Journal of Interventional Cardiac Electrophysiology : an International Journal of Arrhythmias and Pacing. 2001 December; 5(4): 463-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11752915

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Differentiation of atypical atrioventricular node re-entrant tachycardia from orthodromic reciprocating tachycardia using a septal accessory pathway by the response to ventricular pacing. Author(s): Michaud GF, Tada H, Chough S, Baker R, Wasmer K, Sticherling C, Oral H, Pelosi F Jr, Knight BP, Strickberger SA, Morady F. Source: Journal of the American College of Cardiology. 2001 October; 38(4): 1163-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11583898

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Differentiation of narrow QRS complex tachycardia types using the 12-lead electrocardiogram. Author(s): Erdinler I, Okmen E, Oguz E, Akyol A, Gurkan K, Ulufer T. Source: Annals of Noninvasive Electrocardiology : the Official Journal of the International Society for Holter and Noninvasive Electrocardiology, Inc. 2002 April; 7(2): 120-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12049683

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Diltiazem to treat sinus tachycardia in critically ill patients: a four-year experience. Author(s): Gabrielli A, Gallagher TJ, Caruso LJ, Bennett NT, Layon AJ. Source: Critical Care Medicine. 2001 October; 29(10): 1874-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11588443

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Discrimination of ventricular tachycardia from supraventricular tachycardia by a downloaded wavelet-transform morphology algorithm: a paradigm for development of implantable cardioverter defibrillator detection algorithms. Author(s): Swerdlow CD, Brown ML, Lurie K, Zhang J, Wood NM, Olson WH, Gillberg JM. Source: Journal of Cardiovascular Electrophysiology. 2002 May; 13(5): 432-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12030523

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Dissimilar atrial rhythms: coexistence of reentrant atrial tachycardia, atrioventricular nodal reentrant tachycardia and interatrial conduction block. Author(s): Schreieck J, Zrenner B, Dong J, Ndrepepa G, Schmitt C. Source: Zeitschrift Fur Kardiologie. 2002 January; 91(1): 68-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11963210

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Distinction between atrioventricular reciprocating tachycardia and atrioventricular node re-entrant tachycardia in the adult population based on P wave location; should we reconsider the value of some ECG criteria according to gender and age? Author(s): Maury P, Zimmermann M, Metzger J. Source: Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology. 2003 January; 5(1): 57-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12504642

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Does tachycardia correlate with hypotension after trauma? Author(s): Victorino GP, Battistella FD, Wisner DH. Source: Journal of the American College of Surgeons. 2003 May; 196(5): 679-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12742195

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Dual-loop intra-atrial re-entry tachycardia in a patient with ischaemic cardiomyopathy. Author(s): Ott P. Source: Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology. 2002 April; 4(2): 207-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12135255

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ECG of the month. Idiopathic ventricular tachycardia with a left bundle branch block morphology and right axis deviation. Author(s): Belhassen B, Glick A, Herz I, Berger M, Swissa M. Source: Isr Med Assoc J. 2003 September; 5(9): 679-80. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14509167

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ECG of the month. Regular wide-QRS tachycardia. Ventricular tachycardia. Author(s): Glancy DL, Mendoza D, Starnes S, Mills TA, Greer RW. Source: J La State Med Soc. 2003 May-June; 155(3): 125-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12873094

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Effect of beta-blocking therapy on outcome in the Multicenter UnSustained Tachycardia Trial (MUSTT). Author(s): Ellison KE, Hafley GE, Hickey K, Kellen J, Coromilas J, Stein KM, Lee KL, Buxton AE; Multicenter UnSustained Tachycardia Trial Investigators. Source: Circulation. 2002 November 19; 106(21): 2694-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12438295

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Effect of elevated heart rate preceding the onset of ventricular tachycardia on antitachycardia pacing effectiveness in patients with implantable cardioverter defibrillators. Author(s): Kouakam C, Lauwerier B, Klug D, Jarwe M, Marquie C, Lacroix D, Kacet S. Source: The American Journal of Cardiology. 2003 July 1; 92(1): 26-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12842240

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Effect of radiofrequency catheter ablation of ventricular tachycardia on left ventricular function in patients with prior myocardial infarction. Author(s): Khan HH, Maisel WH, Ho C, Suzuki M, Soejima K, Solomon S, Stevenson WG. Source: Journal of Interventional Cardiac Electrophysiology : an International Journal of Arrhythmias and Pacing. 2002 December; 7(3): 243-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12510135

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Electroanatomic mapping of the endocardium. Implication for catheter ablation of ventricular tachycardia. Author(s): Wetzel U, Hindricks G, Dorszewski A, Schirdewahn P, Gerds-Li JH, Piorkowski C, Kobza R, Tanner H, Kottkamp H. Source: Herz. 2003 November; 28(7): 583-90. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14689118

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Electrocardiographic criteria still useful for mapping of idiopathic right ventricular tachycardia. Author(s): Mounsey JP. Source: Journal of Cardiovascular Electrophysiology. 2003 January; 14(1): 8-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12625603

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Electrocardiographic differentiation of typical atrioventricular node reentrant tachycardia from atrioventricular reciprocating tachycardia mediated by concealed accessory pathway in children. Author(s): Jaeggi ET, Gilljam T, Bauersfeld U, Chiu C, Gow R. Source: The American Journal of Cardiology. 2003 May 1; 91(9): 1084-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12714151

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Electrocardiographic manifestations: wide complex tachycardia due to accessory pathway. Author(s): Nelson JA, Knowlton KU, Harrigan R, Pollack ML, Chan TC. Source: The Journal of Emergency Medicine. 2003 April; 24(3): 295-301. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12676301

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Electrophysiological and electrocardiographic characteristics of focal atrial tachycardia originating from the pulmonary veins: acute and long-term outcomes of radiofrequency ablation. Author(s): Kistler PM, Sanders P, Fynn SP, Stevenson IH, Hussin A, Vohra JK, Sparks PB, Kalman JM. Source: Circulation. 2003 October 21; 108(16): 1968-75. Epub 2003 Oct 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14557361

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Electrophysiological features of orthodromic atrioventricular reentry tachycardia in patients with wolff-Parkinson-white syndrome and atrial fibrillation. Author(s): Kalarus Z, Kowalski O, Lenarczyk R, Prokopczuk J, Pasyk S. Source: Pacing and Clinical Electrophysiology : Pace. 2003 July; 26(7 Pt 1): 1479-88. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12914625

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Electrophysiology of inducible atrial flutter in patients with atrioventricular nodal reentrant tachycardia. Author(s): Liu S, Yuan S, Hertervig E, Kongstad O, Ljungstrom E, Bertil Olsson S. Source: Clinical Physiology and Functional Imaging. 2004 January; 24(1): 19-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14717744

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Electrophysiology of ventricular tachycardia: a historical perspective. Author(s): Josephson ME. Source: Pacing and Clinical Electrophysiology : Pace. 2003 October; 26(10): 2052-67. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14516353

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Electrophysiology of ventricular tachycardia: an historical perspective. Author(s): Josephson ME. Source: Journal of Cardiovascular Electrophysiology. 2003 October; 14(10): 1134-48. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14521677

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Elevated troponin levels in absence of coronary artery disease after supraventricular tachycardia. Author(s): Zellweger MJ, Schaer BA, Cron TA, Pfisterer ME, Osswald S. Source: Swiss Medical Weekly : Official Journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology. 2003 August 9; 133(31-32): 439-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14562187

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Endocardial mapping of right ventricular outflow tract tachycardia using noncontact activation mapping. Author(s): Ribbing M, Wasmer K, Monnig G, Kirchhof P, Loh P, Breithardt G, Haverkamp W, Eckardt L. Source: Journal of Cardiovascular Electrophysiology. 2003 June; 14(6): 602-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12875421

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Epidural haematoma presenting as polymorphic ventricular tachycardia. Author(s): Webb TR, Morgan JM, Roberts PR. Source: Heart (British Cardiac Society). 2003 March; 89(3): 316. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12591840

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Evidence that nonsustained polymorphic ventricular tachycardia causes syncope (data from implantable cardioverter defibrillators). Author(s): Farmer DM, Swygman CA, Wang PJ, Mark Estes NA 3rd, Link MS. Source: The American Journal of Cardiology. 2003 March 1; 91(5): 606-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12615273

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Excessive charge time delaying ventricular tachycardia therapy. Author(s): Panchal VR, Groh WJ. Source: Journal of Cardiovascular Electrophysiology. 2001 September; 12(9): 1078-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11573700

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Extracorporeal life support as a treatment of supraventricular tachycardia in infants. Author(s): Walker GM, McLeod K, Brown KL, Franklin O, Goldman AP, Davis C. Source: Pediatric Critical Care Medicine : a Journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. 2003 January; 4(1): 52-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12656543

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Familial hypertrophic cardiomyopathy-linked mutant troponin T causes stressinduced ventricular tachycardia and Ca2+-dependent action potential remodeling. Author(s): Knollmann BC, Kirchhof P, Sirenko SG, Degen H, Greene AE, Schober T, Mackow JC, Fabritz L, Potter JD, Morad M. Source: Circulation Research. 2003 March 7; 92(4): 428-36. Epub 2003 February 06. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12600890

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Familial orthostatic tachycardia due to norepinephrine transporter deficiency. Author(s): Robertson D, Flattem N, Tellioglu T, Carson R, Garland E, Shannon JR, Jordan J, Jacob G, Blakely RD, Biaggioni I. Source: Annals of the New York Academy of Sciences. 2001 June; 940: 527-43. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11458707

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Familial polymorphic ventricular tachycardia--intracellular calcium channel disorder. Author(s): Swan H, Laitinen PJ. Source: Cardiac Electrophysiology Review. 2002 February; 6(1-2): 81-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11984023

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Fascicular tachycardia: uncommon or just unrecognised? Author(s): Eynon CA, Howe L, Firoozan S. Source: Emergency Medicine Journal : Emj. 2002 September; 19(5): 477-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12205019

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Fast pathway ablation in patients with common atrioventricular nodal reentrant tachycardia and prolonged PR interval during sinus rhythm. Author(s): Reithmann C, Hoffmann E, Grunewald A, Nimmermann P, Remp T, Dorwarth U, Steinbeck G. Source: European Heart Journal. 1998 June; 19(6): 929-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9651718

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Feasibility of a noncontact catheter for endocardial mapping of human ventricular tachycardia. Author(s): Schilling RJ, Peters NS, Davies DW. Source: Circulation. 1999 May 18; 99(19): 2543-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10330386

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Fetal hydrops due to supraventricular tachycardia--successful outcome in a difficult case. Author(s): Doherty G, Bali S, Casey F. Source: Ir Med J. 2003 February; 96(2): 52-3. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12674156

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Fetal supraventricular tachycardia diagnosed and treated at 13 weeks of gestation: a case report. Author(s): Porat S, Anteby EY, Hamani Y, Yagel S. Source: Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. 2003 March; 21(3): 302-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12666229

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Filtered QRS duration on signal-averaged electrocardiography predicts inducibility of ventricular tachycardia in arrhythmogenic right ventricle dysplasia. Author(s): Nasir K, Tandri H, Rutberg J, Tichnell C, Spevak P, Crossan J, Baughman KL, Kasper EK, Tomaselli GF, Berger R, Calkins H. Source: Pacing and Clinical Electrophysiology : Pace. 2003 October; 26(10): 1955-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14516335

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Flecainide and sotalol: a new combination therapy for refractory supraventricular tachycardia in children <1 year of age. Author(s): Price JF, Kertesz NJ, Snyder CS, Friedman RA, Fenrich AL. Source: Journal of the American College of Cardiology. 2002 February 6; 39(3): 517-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11823091

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Flecainide in the intrauterine treatment of fetal supraventricular tachycardia. Author(s): Krapp M, Baschat AA, Gembruch U, Geipel A, Germer U. Source: Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. 2002 February; 19(2): 158-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11876808

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Flecainide induced ventricular tachycardia (torsades de pointes). Author(s): Thevenin J, Da Costa A, Roche F, Romeyer C, Messier M, Isaaz K. Source: Pacing and Clinical Electrophysiology : Pace. 2003 September; 26(9): 1907-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12930510

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Flumazenil is innocuous in a paroxysmal supraventricular tachycardia and radiofrequency ablation: a paediatric case report and review of the literature. Author(s): Weinbroum AA, Glick A, Belhassen B. Source: Paediatric Anaesthesia. 2003 May; 13(4): 349-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12753451

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Fluoroscopic cardiac anatomy for catheter ablation of tachycardia. Author(s): Farre J, Anderson RH, Cabrera JA, Sanchez-Quintana D, Rubio JM, Romero J, Cabestrero F. Source: Pacing and Clinical Electrophysiology : Pace. 2002 January; 25(1): 76-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11877940

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Focal atrial tachycardia arising from the mitral annulus: electrocardiographic and electrophysiologic characterization. Author(s): Kistler PM, Sanders P, Hussin A, Morton JB, Vohra JK, Sparks PB, Kalman JM. Source: Journal of the American College of Cardiology. 2003 June 18; 41(12): 2212-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12821250

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Focal atrial tachycardia originating from the musculature of the coronary sinus. Author(s): Volkmer M, Antz M, Hebe J, Kuck KH. Source: Journal of Cardiovascular Electrophysiology. 2002 January; 13(1): 68-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11843486

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Four faces of baroreflex failure: hypertensive crisis, volatile hypertension, orthostatic tachycardia, and malignant vagotonia. Author(s): Ketch T, Biaggioni I, Robertson R, Robertson D. Source: Circulation. 2002 May 28; 105(21): 2518-23. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12034659

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Frequency and characteristics of progressive aberrancy during supraventricular tachycardia. Author(s): Betts TR, Goldberger JJ, Kadish AH. Source: The American Journal of Cardiology. 2003 September 15; 92(6): 736-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12972123

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Frequency of late recurrence of intra-atrial reentry tachycardia after radiofrequency catheter ablation in patients with congenital heart disease. Author(s): Kannankeril PJ, Anderson ME, Rottman JN, Wathen MS, Fish FA. Source: The American Journal of Cardiology. 2003 October 1; 92(7): 879-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14516900

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Frequency of recurrence among infants with supraventricular tachycardia and comparison of recurrence rates among those with and without preexcitation and among those with and without response to digoxin and/or propranolol therapy. Author(s): Tortoriello TA, Snyder CS, Smith EO, Fenrich AL Jr, Friedman RA, Kertesz NJ. Source: The American Journal of Cardiology. 2003 November 1; 92(9): 1045-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14583354

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Gatifloxacin-induced QTc prolongation and ventricular tachycardia. Author(s): Lannini PB, Circiumaru I. Source: Pharmacotherapy. 2001 March; 21(3): 361-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11253862

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Gender and atrioventricular conduction properties of patients with symptomatic atrioventricular nodal reentrant tachycardia and Wolff-Parkinson-White syndrome. Author(s): Liu S, Yuan S, Hertervig E, Kongstad O, Olsson SB. Source: Journal of Electrocardiology. 2001 October; 34(4): 295-301. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11590556

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Gender differences in idiopathic ventricular tachycardia: enhancing the differences. Author(s): Lamberti F. Source: Journal of Cardiovascular Electrophysiology. 2002 July; 13(7): 639-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12139283

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Gender differences in various types of idiopathic ventricular tachycardia. Author(s): Nakagawa M, Takahashi N, Nobe S, Ichinose M, Ooie T, Yufu F, Shigematsu S, Hara M, Yonemochi H, Saikawa T. Source: Journal of Cardiovascular Electrophysiology. 2002 July; 13(7): 633-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12139282

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Genetics of ventricular tachycardia. Author(s): Napolitano C, Priori SG. Source: Current Opinion in Cardiology. 2002 May; 17(3): 222-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12015470

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Giant fibroma with ventricular tachycardia in an elderly patient. Author(s): Kusano KF, Haraoka K, Ohta K, Ohe T. Source: Journal of Cardiovascular Electrophysiology. 2002 July; 13(7): 730. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12139302

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Haemodynamic and catecholamine response to simulated ventricular tachycardia in man: effect of baseline left ventricular function. Author(s): Kolettis TM, Psarros E, Kyriakides ZS, Katsouras CS, Michalis LK, Sideris DA. Source: Heart (British Cardiac Society). 2003 March; 89(3): 306-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12591837

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Heart rate and plasma cyclic AMP responses to isoproterenol infusion and effect of beta-adrenergic blockade in patients with postural orthostatic tachycardia syndrome. Author(s): Abe H, Nagatomo T, Kohshi K, Numata T, Kikuchi K, Sonoda S, Mizuki T, Kuroiwa A, Nakashima Y. Source: Journal of Cardiovascular Pharmacology. 2000; 36 Suppl 2: S79-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11206727

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Heart rate of Japanese male ama divers during breath-hold dives: diving bradycardia or exercise tachycardia? Author(s): Shiraki K, Elsner R, Sagawa S, Torii R, Mohri M, Yamaguchi H. Source: Undersea & Hyperbaric Medicine : Journal of the Undersea and Hyperbaric Medical Society, Inc. 2002 Spring; 29(1): 59-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12507186

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Heart rate variability before the onset of ventricular tachycardia: differences between slow and fast arrhythmias. Author(s): Meyerfeldt U, Wessel N, Schutt H, Selbig D, Schumann A, Voss A, Kurths J, Ziehmann C, Dietz R, Schirdewan A. Source: International Journal of Cardiology. 2002 August; 84(2-3): 141-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12127366

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Heart rate variability patterns before ventricular tachycardia onset in patients with an implantable cardioverter defibrillator. Participating Investigators of ICD-HRV Italian Study Group. Author(s): Lombardi F, Porta A, Marzegalli M, Favale S, Santini M, Vincenti A, De Rosa A; Implantable Cardioverter Defibrillator-Heart Rate Variability Italian Study Group. Source: The American Journal of Cardiology. 2000 November 1; 86(9): 959-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11053707

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Heart rate-dependent electrocardiogram abnormalities in patients with postural tachycardia syndrome. Author(s): Singer W, Shen WK, Opfer-Gehrking TL, McPhee BR, Hilz MJ, Low PA. Source: Autonomic Neuroscience : Basic & Clinical. 2003 January 31; 103(1-2): 106-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12531404

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Heterogeneity of the fast pathway in AV nodal re-entrant tachycardia. An additional layer of complexity. Author(s): Wallis WR, Nathan AW. Source: International Journal of Cardiology. 2000 November-December; 76(2-3): 114-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11104864

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Heterogeneous loss of connexin43 protein in nonischemic dilated cardiomyopathy with ventricular tachycardia. Author(s): Kitamura H, Ohnishi Y, Yoshida A, Okajima K, Azumi H, Ishida A, Galeano EJ, Kubo S, Hayashi Y, Itoh H, Yokoyama M. Source: Journal of Cardiovascular Electrophysiology. 2002 September; 13(9): 865-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12380923

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89

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High-resolution mapping of tachycardia originating from the superior vena cava: evidence of electrical heterogeneity, slow conduction, and possible circus movement reentry. Author(s): Shah DC, Haissaguerre M, Jais P, Clementy J. Source: Journal of Cardiovascular Electrophysiology. 2002 April; 13(4): 388-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12033357

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Histopathological correlation of ablation lesions guided by noncontact mapping in a patient with peripartum cardiomyopathy and ventricular tachycardia. Author(s): Palma EC, Saxenberg V, Vijayaraman P, Ferrick KJ, Gross JN, Kim SG, Fisher JD. Source: Pacing and Clinical Electrophysiology : Pace. 2001 December; 24(12): 1812-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11817817

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How is atrial tachycardia differentiated from atrial flutter? Author(s): Ide B, Drew BJ. Source: Progress in Cardiovascular Nursing. 2000 Fall; 15(4): 151, 153. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11098529

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How may we evaluate and treat a wide-complex tachycardia in a patient presenting with chest pain in the emergency department? Author(s): Thompson C, Tsiperfal A. Source: Progress in Cardiovascular Nursing. 2002 Winter; 17(1): 49-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11872982

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How to ablate typical 'slow/fast' AV nodal reentry tachycardia. Author(s): Heidbuchel H. Source: Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology. 2000 January; 2(1): 15-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11225592

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How to approach epicardial ventricular tachycardia: electroanatomical mapping and ablation by transpericardial nonsurgical approach. Author(s): De Ponti R, Tritto M, Marazzi R, Salerno-Uriarte JA. Source: Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology. 2003 January; 5(1): 55-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12504641

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How to diagnose, locate, and ablate coronary cusp ventricular tachycardia. Author(s): Hachiya H, Aonuma K, Yamauchi Y, Igawa M, Nogami A, Iesaka Y. Source: Journal of Cardiovascular Electrophysiology. 2002 June; 13(6): 551-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12108495

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How to map and ablate atrial scar macroreentrant tachycardia of the right atrium. Author(s): Cosio FG, Pastor A, Nunez A, Montero MA. Source: Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology. 2000 July; 2(3): 193-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11227588

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Hydatid cyst of heart presenting as ventricular tachycardia. Author(s): Yadav BS, Garg N, Raj D. Source: J Assoc Physicians India. 1999 March; 47(3): 342-3. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10999135

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Hyperkalemia and ventricular tachycardia in ELBW infant. Author(s): Singh D, Dutta S, Narang A. Source: Indian Pediatrics. 2003 January; 40(1): 64-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12554924

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Hyperkalemia induced pacemaker far-field endless loop tachycardia. Author(s): Barold SS. Source: Pacing and Clinical Electrophysiology : Pace. 2001 September; 24(9 Pt 1): 1425-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11584470

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Hyperventilation facilitates induction of supraventricular tachycardia: a novel method and the possible mechanism. Author(s): Chen CC, Chen SA, Tai CT, Kuo TB, Chang MS, Prystowsky EN. Source: Journal of Cardiovascular Electrophysiology. 2001 November; 12(11): 1242-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11761410

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Identification and management of ventricular tachycardia. Author(s): Naik N, Talwar KK. Source: J Indian Med Assoc. 2003 February; 101(2): 62-5, 95. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12841484

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91

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Identification of ventricular tachycardia of epicardial origin from unipolar potentials obtained at the endocardial surface: is it feasible? Author(s): Lacroix D, Klug D, Marquie C, Kouakam C, Grandmougin D, Kacet S. Source: Pacing and Clinical Electrophysiology : Pace. 2002 November; 25(11): 1561-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12494612

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Idiopathic cardiomyopathy and recurrent wide QRS tachycardia. Author(s): Delacretaz E, Fuhrer J, Mohacsi P. Source: Pacing and Clinical Electrophysiology : Pace. 2003 June; 26(6): 1407-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12822757

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Idiopathic left bundle-branch block-shaped ventricular tachycardia may originate above the pulmonary valve. Author(s): Timmermans C, Rodriguez LM, Crijns HJ, Moorman AF, Wellens HJ. Source: Circulation. 2003 October 21; 108(16): 1960-7. Epub 2003 Oct 06. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14530199

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Idiopathic left ventricular tachycardia: assessment and treatment. Author(s): Nogami A. Source: Cardiac Electrophysiology Review. 2002 December; 6(4): 448-57. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12438827

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Imitating ventricular tachycardia. Author(s): Bauer A, Schmidt G. Source: Heart (British Cardiac Society). 2003 December; 89(12): 1382. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14617537

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Incessant monomorphic ventricular tachycardia during febrile illness in a patient with Brugada syndrome: fatal electrical storm. Author(s): Dinckal MH, Davutoglu V, Akdemir I, Soydinc S, Kirilmaz A, Aksoy M. Source: Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology. 2003 July; 5(3): 257-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12842640

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Incessant nonreentrant tachycardia due to simultaneous conduction over dual atrioventricular nodal pathways mimicking atrial fibrillation in patients referred for pulmonary vein isolation. Author(s): Mansour M, Marrouche N, Ruskin J, Natale A, Keane D. Source: Journal of Cardiovascular Electrophysiology. 2003 July; 14(7): 752-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12930257

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Inconsistent finding of tachycardia in World War II combat casualties. Author(s): Bellamy RF. Source: Journal of the American College of Surgeons. 2003 October; 197(4): 697. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14522342

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Increase in ventricular tachycardia frequency after biventricular implantable cardioverter defibrillator upgrade. Author(s): Guerra JM, Wu J, Miller JM, Groh WJ. Source: Journal of Cardiovascular Electrophysiology. 2003 November; 14(11): 1245-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14678142

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Increased sympathetic nervous system activity as cause of exercise-induced ventricular tachycardia in patients with normal coronary arteries. Author(s): Ozdemir O, Soylu M, Demir AD, Topaloglu S, Alyan O, Geyik B, Kutuk E. Source: Texas Heart Institute Journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital. 2003; 30(2): 100-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12809249

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Incremental programming of atrial anti-tachycardia pacing therapies in bradycardiaindicated patients: effects on therapy efficacy and atrial tachyarrhythmia burden. Author(s): Hugl B, Israel CW, Unterberg C, Lawo T, Geller JC, Kennis IM, Euler DE, Koehler JL, Hettrick DA; AT500 Verification Study Investigators. Source: Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology. 2003 October; 5(4): 403-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14753639

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Inducible atrioventricular nodal reentry tachycardia in infants with a history of neonatal orthodromic reciprocating tachycardia. Author(s): Kannankeril PJ, Johns JA, Fish FA. Source: Pacing and Clinical Electrophysiology : Pace. 2003 August; 26(8): 1735-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12877708

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Initiation of monomorphic ventricular tachycardia: electrophysiological, clinical features, and drug therapy in patients with implantable defibrillators. Author(s): Gorenek B, Kudaiberdieva G, Birdane A, Goktekin O, Cavusoglu Y, Bakar S, Unalir A, Ata N, Timuralp B. Source: Journal of Electrocardiology. 2003 July; 36(3): 213-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12942483

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93

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Inside or out? Another option for incessant ventricular tachycardia. Author(s): Stevenson WG, Soejima K. Source: Journal of the American College of Cardiology. 2003 June 4; 41(11): 2044-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12798579

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Intra-operative tachycardia and peri-operative outcome. Author(s): Hartmann B, Junger A, Rohrig R, Klasen J, Jost A, Benson M, Braun H, Fuchs C, Hempelmann G. Source: Langenbeck's Archives of Surgery / Deutsche Gesellschaft Fur Chirurgie. 2003 September; 388(4): 255-60. Epub 2003 August 14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12920601

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Intravenous flecainide for the treatment of junctional ectopic tachycardia after surgery for congenital heart disease. Author(s): Bronzetti G, Formigari R, Giardini A, Frascaroli G, Gargiulo G, Picchio FM. Source: The Annals of Thoracic Surgery. 2003 July; 76(1): 148-51; Discussion 151. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12842529

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Irregular wide complex tachycardia. Author(s): Indik JH. Source: Cardiology in Review. 2003 January-February; 11(1): 1-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12493128

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Is it safe to program a long tachycardia detection interval? Author(s): Kuhlkamp V, Dornberger V, Bosch RR, Kettering K, Mewis C. Source: Journal of Cardiovascular Electrophysiology. 2002 November; 13(11): 1169-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12475111

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Is the fascicle of left bundle branch involved in the reentrant circuit of verapamilsensitive idiopathic left ventricular tachycardia? Author(s): Kuo JY, Tai CT, Chiang CE, Yu WC, Huang JL, Hsieh MH, Hou CJ, Tsai CH, Ding YA, Chen SA. Source: Pacing and Clinical Electrophysiology : Pace. 2003 October; 26(10): 1986-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14516339

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Junctional ectopic tachycardia evolving into complete heart block. Author(s): Henneveld H, Hutter P, Bink-Boelkens M, Sreeram N. Source: Heart (British Cardiac Society). 1998 December; 80(6): 627-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10065037

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Junctional ectopic tachycardia in association with blunt abdominal trauma. Author(s): Cloutier RL, Mehr MF, Lin RJ, Tanel RE. Source: Annals of Emergency Medicine. 2002 September; 40(3): 308-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12192355

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Junctional rhythm during slow pathway radiofrequency ablation in patients with atrioventricular nodal reentrant tachycardia: beat-to-beat analysis and its prognostic value in relation to electrophysiologic and anatomic parameters. Author(s): Poret P, Leclercq C, Gras D, Mansour H, Fauchier L, Daubert C, Mabo P. Source: Journal of Cardiovascular Electrophysiology. 2000 April; 11(4): 405-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10809493

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Junctional tachycardia during radiofrequency ablation of the slow pathway in patients with AV nodal reentrant tachycardia: effects of autonomic blockade. Author(s): Chen MC, Guo GB. Source: Journal of Cardiovascular Electrophysiology. 1999 January; 10(1): 56-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9930910

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Lack of benefit of very short basic drive train cycle length or repetition of extrastimulus coupling intervals for induction of ventricular tachycardia. Author(s): Lee CS, Wan SH, Cooper MJ, Ross DL. Source: Journal of Cardiovascular Electrophysiology. 1998 June; 9(6): 574-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9654221

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Late clinical outcome after radiofrequency catheter ablation of idiopathic ventricular tachycardia: follow-up study. Author(s): Petrac D, Radic B, Vukosavic D, Birtic K. Source: Croatian Medical Journal. 2002 February; 43(1): 20-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11828553

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Late QRS activity in signal-averaged magnetocardiography, body surface potential mapping, and orthogonal ECG in postinfarction ventricular tachycardia patients. Author(s): Korhonen P, Tierala I, Simelius K, Vaananen H, Makijarvi M, Nenonen J, Katila T, Toivonen L. Source: Annals of Noninvasive Electrocardiology : the Official Journal of the International Society for Holter and Noninvasive Electrocardiology, Inc. 2002 October; 7(4): 389-98. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12431319

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95

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Latent Mahaim fiber as a cause of antidromic reciprocating tachycardia: recognition and successful radiofrequency ablation. Author(s): Davidson NC, Morton JB, Sanders P, Kalman J. Source: Journal of Cardiovascular Electrophysiology. 2002 January; 13(1): 74-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11843488

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Left atrial conduction along the coronary sinus during ectopic atrial tachycardia and atrial fibrillation: a study using correlation function analysis. Author(s): Carlson J, Santos S, Platonov PG, Rasmussen OK, Johansson R, Olsson SB. Source: Journal of Cardiovascular Electrophysiology. 2003 October; 14(10 Suppl): S14853. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14760917

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Left atrial function preserves pulmonary circulatory pressure during pacingtachycardia and contributes to exercise capacity in patients with idiopathic dilated cardiomyopathy in sinus rhythm, whose exercise is limited by dyspnea. Author(s): Sasaki T, Kubo T, Miyamoto T, Komamura K, Honda K, Masuyama T, Miyatake K. Source: Circulation Journal : Official Journal of the Japanese Circulation Society. 2002 October; 66(10): 937-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12381089

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Left ventricular epicardial outflow tract tachycardia: a new distinct subgroup of outflow tract tachycardia. Author(s): Tada H, Nogami A, Naito S, Fukazawa H, Horie Y, Kubota S, Okamoto Y, Hoshizaki H, Oshima S, Taniguchi K. Source: Japanese Circulation Journal. 2001 August; 65(8): 723-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11502049

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Left ventricular hamartoma associated with ventricular tachycardia. Author(s): Dinh MH, Galvin JM, Aretz TH, Torchiana DF. Source: The Annals of Thoracic Surgery. 2001 May; 71(5): 1673-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11383821

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Left ventricular outflow tract tachycardia originating from the right coronary cusp: identification of location of origin by endocardial noncontact activation mapping from the right ventricular outflow tract. Author(s): Storey J, Iwasa A, Feld GK. Source: Journal of Cardiovascular Electrophysiology. 2002 October; 13(10): 1050-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12435196

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Levofloxacin induced polymorphic ventricular tachycardia with normal QT interval. Author(s): Paltoo B, O'Donoghue S, Mousavi MS. Source: Pacing and Clinical Electrophysiology : Pace. 2001 May; 24(5): 895-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11388112

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Limb venous compliance in patients with idiopathic orthostatic intolerance and postural tachycardia. Author(s): Freeman R, Lirofonis V, Farquhar WB, Risk M. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 2002 August; 93(2): 63644. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12133874

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Limited predictive value of inducible sustained ventricular tachycardia for future occurrence of spontaneous ventricular tachycardia in patients with coronary artery disease and relatively preserved cardiac function. Author(s): Matsushita T, Chun S, Liem LB, Friday KJ, Sung RJ. Source: Journal of Electrocardiology. 2003 July; 36(3): 205-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12942482

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Local vascular responses affecting blood flow in postural tachycardia syndrome. Author(s): Stewart JM, Medow MS, Montgomery LD. Source: American Journal of Physiology. Heart and Circulatory Physiology. 2003 December; 285(6): H2749-56. Epub 2003 August 14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12919934

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Localizing ventricular tachycardia through entrainment. Author(s): Kuo CT, Luqman N, Lin KH, Chiang CW. Source: Chang Gung Med J. 2000 December; 23(12): 725-37. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11416893

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Location of accessory connection in infants presenting with supraventricular tachycardia in utero: clinical correlations. Author(s): Kannankeril PJ, Gotteiner NL, Deal BJ, Johnsrude CL, Strasburger JF. Source: American Journal of Perinatology. 2003 April; 20(3): 115-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12802710

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Long RP tachycardia after injury of accessory atrioventricular pathway conduction by radiofrequency catheter ablation. Author(s): Chen HY, Tai CT, Chen SA. Source: Pacing and Clinical Electrophysiology : Pace. 2003 March; 26(3): 765-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12698679

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97

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Long-term experience with the electrogram (EGM) width criterion for differential of supraventricular tachycardia (SVT) and ventricular tachycardia (VT) in patients with implantable cardioverter defibrillators (ICDs). Author(s): Duru F, Candinas R. Source: Pacing and Clinical Electrophysiology : Pace. 2001 July; 24(7): 1171-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11475840

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Long-term follow-up after radiofrequency catheter ablation of ventricular tachycardia: a successful approach? Author(s): Borger van der Burg AE, de Groot NM, van Erven L, Bootsma M, van der Wall EE, Schalij MJ. Source: Journal of Cardiovascular Electrophysiology. 2002 May; 13(5): 417-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12030520

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Long-term follow-up of fast pathway radiofrequency ablation in atrioventricular nodal reentrant tachycardia. Author(s): Lickfett L, Pfeiffer D, Schimpf R, Calkins H, Luderitz B, Lewalter T. Source: The American Journal of Cardiology. 2002 May 1; 89(9): 1124-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11988207

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Long-term outcomes on quality-of-life and health care costs in patients with supraventricular tachycardia (radiofrequency catheter ablation versus medical therapy). Author(s): Goldberg AS, Bathina MN, Mickelsen S, Nawman R, West G, Kusumoto FM. Source: The American Journal of Cardiology. 2002 May 1; 89(9): 1120-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11988206

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Magnetic electroanatomic mapping of an atrial tachycardia requiring ablation within the coronary sinus. Author(s): Navarrete AJ, Arora R, Hubbard JE, Miller JM. Source: Journal of Cardiovascular Electrophysiology. 2003 December; 14(12): 1361-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14678114

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Magnetocardiographic rhythm patterns at initiation and termination of fetal supraventricular tachycardia. Author(s): Wakai RT, Strasburger JF, Li Z, Deal BJ, Gotteiner NL. Source: Circulation. 2003 January 21; 107(2): 307-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12538433

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Management of ventricular fibrillation or unstable ventricular tachycardia in patients with congenital long-QT syndrome: a suggested modification to ACLS guidelines. Author(s): Homme JH, White RD, Ackerman MJ. Source: Resuscitation. 2003 October; 59(1): 111-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14580741

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Mapping for ventricular tachycardia. Author(s): Dixit S, Callans DJ. Source: Cardiac Electrophysiology Review. 2002 December; 6(4): 436-41. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12438825

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Massive left atrial appendage aneurysm presenting as supraventricular tachycardia. Author(s): Chockalingam A, Alagesan R, Nandakumar M, Gnanavelu G. Source: Indian Heart J. 2003 July-August; 55(4): 379-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14686673

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Mechanisms of monomorphic ventricular tachycardia in coronary artery disease. Author(s): Lazzara R, Scherlag BJ. Source: Journal of Interventional Cardiac Electrophysiology : an International Journal of Arrhythmias and Pacing. 2003 April; 8(2): 87-92. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12766499

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Methemoglobinemia induced by refrigerated vegetable puree in conjunction with supraventricular tachycardia. Author(s): Bryk T, Zalzstein E, Lifshitz M. Source: Acta Paediatrica (Oslo, Norway : 1992). 2003 October; 92(10): 1214-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14632342

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Microvascular filtration is increased in postural tachycardia syndrome. Author(s): Stewart JM. Source: Circulation. 2003 June 10; 107(22): 2816-22. Epub 2003 May 19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12756156

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Modification and ablation for inappropriate sinus tachycardia: current status. Author(s): Shen WK. Source: Cardiac Electrophysiology Review. 2002 December; 6(4): 349-55. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12438812

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Modification to the Fontan procedure for the prophylaxis of intra-atrial reentrant tachycardia: short-term results of a prospective randomized blinded trial. Author(s): Collins KK, Rhee EK, Delucca JM, Alexander ME, Bevilacqua LM, Berul CI, Walsh EP, Mayer JE, Jonas RA, del Nido PJ, Triedman JK. Source: The Journal of Thoracic and Cardiovascular Surgery. 2004 March; 127(3): 721-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15001900

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Multiple AV nodal pathways in patients with AV nodal reentrant tachycardia--more common than expected? Author(s): Heinroth KM, Kattenbeck K, Stabenow I, Trappe HJ, Weismuller P. Source: Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology. 2002 October; 4(4): 375-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12408257

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Muscle sympathetic nerve traffic during spontaneous- versus adenosine-mediated termination of idiopathic right ventricular outflow tract tachycardia. Author(s): Slotwiner DJ, Christini DJ, Stein KM, Markowitz SM, Mittal S, Iwai S, Das MK, Lerman BB. Source: The American Journal of Cardiology. 2003 January 1; 91(1): 86-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12505580

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Myopotential interference with a unipolar VDD pacemaker presenting with tachycardia and transient ventricular asystole. Author(s): Liang HY, Lee CS, Lin CC, Chen YF. Source: Kaohsiung J Med Sci. 2002 December; 18(12): 632-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12670040

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Narrow QRS tachycardia with negative P waves in leads I and aVL: what is the mechanism? Author(s): Calabro MP, Luzza F, Carerj S, Oreto G. Source: Journal of Cardiovascular Electrophysiology. 2003 September; 14(9): 1013-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12950551

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Narrow-complex tachycardia. Author(s): Bosen D. Source: Nursing. 2003 May; 33(5): 96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12792576

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Neonatal ECG changes caused by supratherapeutic flecainide following treatment for fetal supraventricular tachycardia. Author(s): Rasheed A, Simpson J, Rosenthal E. Source: Heart (British Cardiac Society). 2003 April; 89(4): 470. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12639886

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Neonatal flecainide toxicity following supraventricular tachycardia treatment. Author(s): Hall CM, Ward Platt MP. Source: The Annals of Pharmacotherapy. 2003 September; 37(9): 1343-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12921523

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Nifekalant hydrochloride, a novel class III antiarrhythmic agent, suppressed postoperative recurrent ventricular tachycardia in a patient undergoing coronary artery bypass grafting and the Dor approach. Author(s): Sahara M, Sagara K, Yamashita T, Iinuma H, Fu LT, Watanabe H. Source: Circulation Journal : Official Journal of the Japanese Circulation Society. 2003 August; 67(8): 712-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12890916

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Nonautomatic focal atrial tachycardia: characterization and ablation of a poorly understood arrhythmia in 38 patients. Author(s): Kammeraad JA, Balaji S, Oliver RP, Chugh SS, Halperin BD, Kron J, McAnulty JH. Source: Pacing and Clinical Electrophysiology : Pace. 2003 March; 26(3): 736-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12698675

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Noninvasive diagnosis of dual AV nodal physiology in patients with AV nodal reentrant tachycardia by adenosine triphosphate test. Author(s): Okumura Y, Watanabe I, Oshikawa N, Masaki R, Okubo K, Hashimoto K, Kofune T, Yamada T, Wakita R, Takagi Y, Saito S, Ozawa Y, Kanmatsuse K. Source: Japanese Heart Journal. 2003 September; 44(5): 655-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14587647

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Nonsurgical transthoracic epicardial radiofrequency ablation: an alternative in incessant ventricular tachycardia. Author(s): Brugada J, Berruezo A, Cuesta A, Osca J, Chueca E, Fosch X, Wayar L, Mont L. Source: Journal of the American College of Cardiology. 2003 June 4; 41(11): 2036-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12798578

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101

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Non-sustained ventricular tachycardia in hypertrophic cardiomyopathy: an independent marker of sudden death risk in young patients. Author(s): Monserrat L, Elliott PM, Gimeno JR, Sharma S, Penas-Lado M, McKenna WJ. Source: Journal of the American College of Cardiology. 2003 September 3; 42(5): 873-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12957435

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Nonsustained ventricular tachycardia: another approach. Author(s): Weinberger RL. Source: Postgraduate Medicine. 2003 May; 113(5): 20, 103; Author Reply 103. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12764894

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On ridges, crests, and rings of fire: just location, or does the catheter point to the origins of focal tachycardia? Author(s): Jayachandran JV. Source: Journal of Cardiovascular Electrophysiology. 2001 June; 12(6): 660-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11405399

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Optimized mapping of slow pathway ablation guided by subthreshold stimulation: a randomized prospective study in patients with recurrent atrioventricular nodal reentrant tachycardia. Author(s): Willems S, Weiss C, Shenasa M, Ventura R, Hoffmann M, Meinertz T. Source: Journal of the American College of Cardiology. 2001 May; 37(6): 1645-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11345379

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Orthodromic tachycardia with atrioventricular dissociation: evidence for a nodoventricular (Mahaim) fiber. Author(s): Mantovan R, Verlato R, Corrado D, Buia G, Haissaguerre M, Shah DC. Source: Pacing and Clinical Electrophysiology : Pace. 2000 February; 23(2): 276-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10709239

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Orthostatic headaches without CSF leak in postural tachycardia syndrome. Author(s): Mokri B, Low PA. Source: Neurology. 2003 October 14; 61(7): 980-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14557573

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Orthostatic intolerance and tachycardia associated with norepinephrine-transporter deficiency. Author(s): Shannon JR, Flattem NL, Jordan J, Jacob G, Black BK, Biaggioni I, Blakely RD, Robertson D. Source: The New England Journal of Medicine. 2000 February 24; 342(8): 541-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10684912

102

Tachycardia

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Orthostatic intolerance and the postural tachycardia syndrome: genetic and environment pathophysiologies. Neurolab Autonomic Team. Author(s): Robertson D, Shannon JR, Biaggioni I, Ertl AC, Diedrich A, Carson R, Furlan R, Jacob G, Jordan J; Neurolab Autonomic Team. Source: Pflugers Archiv : European Journal of Physiology. 2000; 441(2-3 Suppl): R48-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11200979

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Outcome of men with ischemic cardiomyopathy, asymptomatic nonsustained ventricular tachycardia, and negative electrophysiologic studies. Author(s): Kim MH, Bruckman D, Kirsh MM, Kou WH. Source: The American Journal of Cardiology. 2000 January 1; 85(1): 119-21, A9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11078253

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Outcomes after radiofrequency catheter ablation of atrial tachycardia. Author(s): Anguera I, Brugada J, Roba M, Mont L, Aguinaga L, Geelen P, Brugada P. Source: The American Journal of Cardiology. 2001 April 1; 87(7): 886-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11274945

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Para-Hisian entrainment: a novel pacing maneuver to differentiate orthodromic atrioventricular reentrant tachycardia from atrioventricular nodal reentrant tachycardia. Author(s): Reddy VY, Jongnarangsin K, Albert CM, Sabbour H, Keane D, Mela T, McGovern B, Ruskin JN. Source: Journal of Cardiovascular Electrophysiology. 2003 December; 14(12): 1321-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14678108

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Paroxysmal supraventricular tachycardia in neonatal tuberous sclerosis complex and cardiac rhabdomyoma: report of one case. Author(s): Yen HR, Chu SM. Source: Acta Paediatr Taiwan. 2003 March-April; 44(2): 112-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12845856

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Paroxysmal ventricular tachycardia due to interventricular hydatid cyst. Author(s): Sagkan O, Kossus A, Demirag MK, Dursun Y, Bahadir H, Yazici M, Keceligil HT. Source: Echocardiography (Mount Kisco, N.Y.). 2002 November; 19(8): 683-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12487638

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Permanent form of junctional reciprocating tachycardia and tachycardia-induced cardiomyopathy treated by catheter ablation: a case report. Author(s): Semizel E, Ayabakan C, Ceviz N, Celiker A. Source: Turk J Pediatr. 2003 October-December; 45(4): 338-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14768801

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103

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Permanent junctional reciprocating tachycardia: an incessant tachycardia in children. Author(s): Trigo C, Paixao A, da Silva MN, Kaku S. Source: Rev Port Cardiol. 2003 June; 22(6): 767-74. English, Portuguese. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14526694

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Pharmacological treatment of young children with permanent junctional reciprocating tachycardia. Author(s): van Stuijvenberg M, Beaufort-Krol GC, Haaksma J, Bink-Boelkens MT. Source: Cardiology in the Young. 2003 October; 13(5): 408-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14694933

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Position dependent ventricular tachycardia in two children with peripherally inserted central catheters (PICCs). Author(s): Hacking MB, Brown J, Chisholm DG. Source: Paediatric Anaesthesia. 2003 July; 13(6): 527-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12846710

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Postoperative junctional ectopic tachycardia in children: incidence, risk factors, and treatment. Author(s): Hoffman TM, Bush DM, Wernovsky G, Cohen MI, Wieand TS, Gaynor JW, Spray TL, Rhodes LA. Source: The Annals of Thoracic Surgery. 2002 November; 74(5): 1607-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12440616

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Primary radiofrequency ablation for incessant idiopathic ventricular tachycardia. Author(s): Gupta AK, Kumar AV, Lokhandwala YY, Vora AM, Maheshwari A, Thakur RK. Source: Pacing and Clinical Electrophysiology : Pace. 2002 November; 25(11): 1555-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12494611

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Pseudo-ventricular tachycardia: electrocardiographic artefact mimicking nonsustained polymorphic ventricular tachycardia in a patient evaluated for syncope. Author(s): Vereckei A. Source: Heart (British Cardiac Society). 2004 January; 90(1): 81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14676251

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QRS and cycle length alternans during paroxysmal supraventricular tachycardia: what is the mechanism? Author(s): Maury P, Raczka F, Piot C, Davy JM. Source: Journal of Cardiovascular Electrophysiology. 2002 January; 13(1): 92-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11843492

104

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QRS complex voltage changes associated with supraventricular tachycardia. Author(s): Oreto G, Luzza F, Badessa F, Calabro MP, Mazzone P, Carerj S, Saporito F, Pappone C. Source: Journal of Cardiovascular Electrophysiology. 2001 December; 12(12): 1358-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11797992

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QT dispersion as a noninvasive predictor of inducible ventricular tachycardia. Author(s): Stoletniy LN, Pai SM, Platt ML, Torres VI, Pai RG. Source: Journal of Electrocardiology. 1999 April; 32(2): 173-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10338036

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QTC interval prolongation and polymorphic ventricular tachycardia in association with levofloxacin. Author(s): Samaha FF. Source: The American Journal of Medicine. 1999 November; 107(5): 528-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10569314

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Quadricuspid aortic valve, parossistyc supraventricular tachycardia and double right kidney: an uncommon association. Author(s): Podesta A, Dottori V, Parodi E, Crivellari R, Regesta T, Passerone GC. Source: Minerva Cardioangiol. 2001 February; 49(1): 75-9. English, Italian. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11279386

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Quality of life before and after radiofrequency catheter ablation in patients with drug refractory atrioventricular nodal reentrant tachycardia. Author(s): Larson MS, McDonald K, Young C, Sung R, Hlatky MA. Source: The American Journal of Cardiology. 1999 August 15; 84(4): 471-3, A9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10468092

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Quality of life in patients with postural tachycardia syndrome. Author(s): Benrud-Larson LM, Dewar MS, Sandroni P, Rummans TA, Haythornthwaite JA, Low PA. Source: Mayo Clinic Proceedings. 2002 June; 77(6): 531-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12059122

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Quantitative comparison of spontaneous and paced 12-lead electrocardiogram during right ventricular outflow tract ventricular tachycardia. Author(s): Gerstenfeld EP, Dixit S, Callans DJ, Rajawat Y, Rho R, Marchlinski FE. Source: Journal of the American College of Cardiology. 2003 June 4; 41(11): 2046-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12798580

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Quantitative effects of functional bundle branch block in patients with atrioventricular reentrant tachycardia. Author(s): Yang Y, Cheng J, Glatter K, Dorostkar P, Modin GW, Scheinman MM. Source: The American Journal of Cardiology. 2000 April 1; 85(7): 826-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10758921

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Questioning your treatment of tachycardia. Author(s): Suprun SC Jr. Source: Emerg Med Serv. 2003 October; 32(10): 58, 61-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14596043

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Radiofrequency ablation of incessant orthodromic tachycardia in a young child with a univentricular heart. Author(s): Gupta AK, Lokhandwala YY. Source: Indian Heart J. 2003 November-December; 55(6): 652-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14989521

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Radiofrequency catheter ablation of accessory pathway-mediated tachycardia is a safe and effective long-term therapy. Author(s): Wang L, Yao R. Source: Archives of Medical Research. 2003 September-October; 34(5): 394-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14602506

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Radiofrequency catheter ablation of fast pathway via unconventional right subclavian venous access for atrioventricular nodal reentrant tachycardia. Author(s): Machado C, Liddon V, Roy D. Source: Journal of Interventional Cardiology. 2003 October; 16(5): 377-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14603794

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Recurrent positional ventricular tachycardia in a patient with carcinoma of the oesophagus. Author(s): Gautam PL, Kathuria S, Sood D, Kaul TJ. Source: Anaesthesia. 2003 January; 58(1): 98. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12492688

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Recurrent ventricular tachycardia of non-ischaemic origin. Author(s): Ng E, Adlam D, Keal RP, Ng GA. Source: Journal of the Royal Society of Medicine. 2004 January; 97(1): 23-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14702359

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Refractory adenosine-sensitive congenital His bundle tachycardia: response to calcium-channel blockers. Author(s): Sharada K, Narasimhan C, Rao KN, Soma Raju B. Source: Indian Heart J. 2003 May-June; 55(3): 259-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14560937

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Regular wide-complex tachycardia recognition. Author(s): Dailey MW. Source: Emerg Med Serv. 2003 October; 32(10): 74-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14596045

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Response to adenosine differentiates focal from macroreentrant atrial tachycardia: validation using three-dimensional electroanatomic mapping. Author(s): Iwai S, Markowitz SM, Stein KM, Mittal S, Slotwiner DJ, Das MK, Cohen JD, Hao SC, Lerman BB. Source: Circulation. 2002 November 26; 106(22): 2793-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12451005

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Reversal of atrial mechanical dysfunction after cardioversion of atrial fibrillation: implications for the mechanisms of tachycardia-mediated atrial cardiomyopathy. Author(s): Sanders P, Morton JB, Kistler PM, Vohra JK, Kalman JM, Sparks PB. Source: Circulation. 2003 October 21; 108(16): 1976-84. Epub 2003 Oct 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14557372

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Role of invasive electrophysiologic testing in the evaluation and management of adult patients with focal junctional tachycardia. Author(s): Hamdan MH, Badhwar N, Scheinman MM. Source: Cardiac Electrophysiology Review. 2002 December; 6(4): 431-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12438824

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Spontaneous resolution of ventricular tachycardia with right bundle branch block morphology: a case report. Author(s): Bostan OM, Celiker A, Ozme S. Source: Turk J Pediatr. 2003 April-June; 45(2): 170-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12921310

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Spontaneous transition of 2:1 atrioventricular block to 1:1 atrioventricular conduction during atrioventricular nodal reentrant tachycardia: evidence supporting the intraHisian or infra-Hisian area as the site of block. Author(s): Lee SH, Tai CT, Chiang CE, Yu WC, Cheng JJ, Ding YA, Chang MS, Chen SA. Source: Journal of Cardiovascular Electrophysiology. 2003 December; 14(12): 1337-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14678110

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Successful radiofrequency catheter ablation therapy of an adolescent with atrial ectopic tachycardia. Author(s): Kafali G, Celiker A, Ozer S. Source: Turk J Pediatr. 2003 October-December; 45(4): 342-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14768802

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Supraventricular tachycardia after fenoterol inhalation: report of two cases. Author(s): Hung YF, Yang W, Chang ML. Source: Acta Paediatr Taiwan. 2003 May-June; 44(3): 165-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14521024

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Supraventricular tachycardia immediately following abolition of preexcitation during RF delivery: AVRT or not? Author(s): Weiss C, Risius T, Willems S. Source: Pacing and Clinical Electrophysiology : Pace. 2002 November; 25(11): 1641-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12494625

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Supraventricular tachycardia in pregnancy. Author(s): Robins K, Lyons G. Source: British Journal of Anaesthesia. 2004 January; 92(1): 140-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14665567

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Supraventricular tachycardia with sudden rate doubling: what is the mechanism? Author(s): Calabro MP, Carbone V, Carerj S, Oreto G. Source: Journal of Cardiovascular Electrophysiology. 2003 October; 14(10): 1126-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14521671

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Supraventricular tachycardia: an incidental diagnosis in infants and difficult to prove in children. Author(s): Vos P, Pulles-Heintzberger CF, Delhaas T. Source: Acta Paediatrica (Oslo, Norway : 1992). 2003 September; 92(9): 1058-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14599070

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Sustained polymorphic ventricular tachycardia unassociated with QT prolongation or bradycardia in the Kearns-Sayre syndrome. Author(s): Oginosawa Y, Abe H, Nagatomo T, Mizuki T, Nakashima Y. Source: Pacing and Clinical Electrophysiology : Pace. 2003 September; 26(9): 1911-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12930512

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Sustained ventricular tachycardia in long QT syndrome: is propofol the culprit? Author(s): Rewari V, Kaul H. Source: Anesthesiology. 2003 September; 99(3): 764. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12960575

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Tachycardia in Ebstein's anomaly. Author(s): Nikolic G. Source: Heart & Lung : the Journal of Critical Care. 2003 September-October; 32(5): 3479. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14528192

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Termination of a narrow QRS-complex tachycardia: what is the mechanism? Author(s): Morady F. Source: Journal of Cardiovascular Electrophysiology. 2003 October; 14(10): 1124-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14521670

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Termination of paroxysmal supraventricular tachycardia by tecadenoson (CVT-510), a novel A1-adenosine receptor agonist. Author(s): Prystowsky EN, Niazi I, Curtis AB, Wilber DJ, Bahnson T, Ellenbogen K, Dhala A, Bloomfield DM, Gold M, Kadish A, Fogel RI, Gonzalez MD, Belardinelli L, Shreeniwas R, Wolff AA. Source: Journal of the American College of Cardiology. 2003 September 17; 42(6): 1098102. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13678937

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The efficacy of bolus administration of landiolol for attenuating tachycardia in pheochromocytoma. Author(s): Nishina K, Mikawa K, Yonemoto Y, Sugimoto Y. Source: Anesthesia and Analgesia. 2004 March; 98(3): 876-7; Author Reply 877-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14980966

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The surface electrocardiographic changes after radiofrequency catheter ablation in patients with idiopathic left ventricular tachycardia. Author(s): Li D, Guo J, Xu Y, Li X. Source: Int J Clin Pract. 2004 January; 58(1): 11-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14994964

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Transition from ventricular fibrillation to ventricular tachycardia: a simulation study on the role of Ca(2+)-channel blockers in human ventricular tissue. Author(s): Bernus O, Van Eyck B, Verschelde H, Panfilov AV. Source: Physics in Medicine and Biology. 2002 December 7; 47(23): 4167-79. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12502041

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Transitory or permanent regular wide QRS complex tachycardia induced by atrial stimulation in patients without apparent heart disease. Significance. Author(s): Brembilla-Perrot B, Beurrier D, Houriez P, Claudon O, Rizk J, Lemoine C, Gregoire P, Nippert M. Source: Annales De Cardiologie Et D'angeiologie. 2003 August; 52(4): 226-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14603703

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Treatment of fetal tachycardia with sotalol: transplacental pharmacokinetics and pharmacodynamics. Author(s): Oudijk MA, Ruskamp JM, Ververs FF, Ambachtsheer EB, Stoutenbeek P, Visser GH, Meijboom EJ. Source: Journal of the American College of Cardiology. 2003 August 20; 42(4): 765-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12932617

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T-wave alternans in patients with right ventricular tachycardia. Author(s): Kinoshita O, Tomita T, Hanaoka T, Tsutsui H, Imamura H, Yazaki Y, Watanabe N, Hongo M, Kubo K. Source: Cardiology. 2003; 100(2): 86-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14557695

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Type I primary hyperoxaluria: an unusual presentation of ventricular tachycardia. Author(s): Quan KJ, Biblo LA. Source: Cardiology in Review. 2003 November-December; 11(6): 318-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14580300

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Unipolar electrogram in identification of successful targets for radiofrequency catheter ablation of focal atrial tachycardia. Author(s): Tang K, Ma J, Zhang S, Chu J, Wang F, Zhang K, Chen X. Source: Chinese Medical Journal. 2003 October; 116(10): 1455-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14570599

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Unusual cause of intraoperative hypertension and tachycardia. Author(s): Unnikrishnan KP, Sinha PK, Neema PK. Source: Anesthesia and Analgesia. 2003 October; 97(4): 1196. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14500184

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Unusual phenomenon of spontaneous termination of atrioventricular nodal reentrant tachycardia with 2:1 atrioventricular block. Author(s): Lin YJ, Tai CT, Chen SA. Source: Journal of Cardiovascular Electrophysiology. 2003 April; 14(4): 437-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12741721

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Use of a modified, commercially available temporary pacemaker for R wave synchronized atrial pacing in postoperative junctional ectopic tachycardia. Author(s): Janousek J, Vojtovic P, Gebauer RA. Source: Pacing and Clinical Electrophysiology : Pace. 2003 February; 26(2 Pt 1): 579-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12710317

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Use of intracardiac echocardiography in guiding radiofrequency catheter ablation of atrial tachycardia in a patient after the senning operation. Author(s): Kedia A, Hsu PY, Holmes J, Burnham D, West G, Kusumoto FM. Source: Pacing and Clinical Electrophysiology : Pace. 2003 November; 26(11): 2178-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14622324

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Usefulness of a ventricular extrastimulus from the summit of the ventricular septum in diagnosis of septal accessory pathway in patients with supraventricular tachycardia. Author(s): Matsushita T, Badhwar N, Collins KK, Van Hare GF, Barbato G, Lee BK, Lee RJ, Scheinman MM. Source: The American Journal of Cardiology. 2004 March 1; 93(5): 643-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14996601

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Usefulness of echocardiography in infants with supraventricular tachycardia. Author(s): Snyder CS, Fenrich AL, Friedman RA, Rosenthal G, Kertesz NJ. Source: The American Journal of Cardiology. 2003 May 15; 91(10): 1277-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12745122

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Usefulness of QRS prolongation in predicting risk of inducible monomorphic ventricular tachycardia in patients referred for electrophysiologic studies. Author(s): Horwich T, Lee SJ, Saxon L. Source: The American Journal of Cardiology. 2003 October 1; 92(7): 804-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14516880

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Usefulness of ST-segment elevation in lead aVR during tachycardia for determining the mechanism of narrow QRS complex tachycardia. Author(s): Ho YL, Lin LY, Lin JL, Chen MF, Chen WJ, Lee YT. Source: The American Journal of Cardiology. 2003 December 15; 92(12): 1424-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14675578

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Utility of a combined signal-averaged electrocardiogram and QT dispersion algorithm in identifying arrhythmogenic right ventricular dysplasia in patients with tachycardia of right ventricular origin. Author(s): Nasir K, Bomma C, Khan FA, Tandri H, Tichnell C, James C, Rutberg J, Berger R, Calkins H. Source: The American Journal of Cardiology. 2003 July 1; 92(1): 105-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12842263

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Ventricular rate stabilization algorithm of ICD causing dual chamber pacing during ventricular tachycardia. Author(s): Barold SS. Source: Journal of Interventional Cardiac Electrophysiology : an International Journal of Arrhythmias and Pacing. 2003 December; 9(3): 397-400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14618063

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Ventricular repolarization change during initiation of supraventricular tachycardia. Author(s): Lin YJ, Tai CT, Chen SA. Source: Journal of Cardiovascular Electrophysiology. 2003 September; 14(9): 1015. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12950552

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Ventricular tachycardia as an electrocardiography artifact during functional endoscopic sinus surgery. Author(s): Gaiser RR, Demetry DJ, Schlosser R. Source: American Journal of Rhinology. 2003 March-April; 17(2): 83-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12751701

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Ventricular tachycardia associated with bidirectional reentrant circuit around the tricuspid annulus in arrhythmogenic right ventricular dysplasia. Author(s): Noda T, Suyama K, Shimizu W, Satomi K, Otomo K, Nakagawa E, Kurita T, Aihara N, Kamakura S. Source: Pacing and Clinical Electrophysiology : Pace. 2003 October; 26(10): 2050-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14516352

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Ventricular tachycardia associated with transmyocardial migration of an epicardial pacing wire. Author(s): Meier DJ, Tamirisa KP, Eitzman DT. Source: The Annals of Thoracic Surgery. 2004 March; 77(3): 1077-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14992934

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Ventricular tachycardia following head injury. Author(s): Khogali SS, Townsend JN, Marshal H. Source: Heart (British Cardiac Society). 2003 August; 89(8): 829. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12860847

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Ventricular tachycardia in nonpostoperative pediatric patients: role of radiofrequency catheter ablation. Author(s): Laohakunakorn P, Paul T, Knick B, Blaufox AD, Long B, Saul JP. Source: Pediatric Cardiology. 2003 March-April; 24(2): 154-60. Epub 2002 December 04. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12457254

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Verapamil sensitive idiopathic ventricular tachycardia in an infant. Author(s): Wang JD, Fu YC, Jan SL, Chi CS. Source: Japanese Heart Journal. 2003 September; 44(5): 667-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14587648

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Verapamil-induced electrical and cycle length alternans during supraventricular tachycardia: what is the mechanism? Author(s): Luzza F, Oreto G. Source: Journal of Cardiovascular Electrophysiology. 2003 March; 14(3): 323-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12716120

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Verapamil-sensitive idiopathic left ventricular tachycardia in pregnancy. Author(s): Cleary-Goldman J, Salva CR, Infeld JI, Robinson JN. Source: J Matern Fetal Neonatal Med. 2003 August;14(2):132-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14629096

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What caused this wide-complex tachycardia? Author(s): Tsiperfal A, Thompson C. Source: Progress in Cardiovascular Nursing. 2003 Fall; 18(4): 201-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14605524

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What is this wide-complex tachycardia and what needs to be done about it? Author(s): Thompson C, Tsiperfal A. Source: Progress in Cardiovascular Nursing. 2001 Fall; 16(4): 176-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11684911

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When does ST-segment depression in the presence of a narrow QRS tachycardia signify ischemia? Author(s): Thompson C, Tsiperfal A. Source: Progress in Cardiovascular Nursing. 2003 Winter; 18(1): 60-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12624574

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Which patient should be referred to an electrophysiologist: supraventricular tachycardia. Author(s): Schilling RJ. Source: Heart (British Cardiac Society). 2002 March; 87(3): 299-304. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11847181

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Wide complex tachycardia and congenital heart disease. Author(s): Surmely JF, Taylor S, Payot M, Delacretaz E. Source: Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology. 2002 January; 4(1): 99-101. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11846323

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Wide complex tachycardia. Author(s): Brown DF, Nadel ES. Source: The Journal of Emergency Medicine. 2001 October; 21(3): 271-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11604282

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Wide QRS complex tachycardia with negative precordial concordance: always a ventricular origin? Author(s): Volders PG, Timmermans C, Rodriguez LM, van Pol PE, Wellens HJ. Source: Journal of Cardiovascular Electrophysiology. 2003 January; 14(1): 109-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12625622

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Wide-complex tachycardia with an abrupt change in cycle length: what is the mechanism? Author(s): Guttigoli A, Mittal S, Stein KM, Lerman BB. Source: Journal of Cardiovascular Electrophysiology. 2003 July; 14(7): 781-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12930261

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Wide-QRS complex tachycardia during pregnancy: treatment with cardioversion and review. Author(s): Oktay C, Kesapli M, Altekin E. Source: The American Journal of Emergency Medicine. 2002 September; 20(5): 492-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12216052

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CHAPTER 2. NUTRITION AND TACHYCARDIA Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and tachycardia.

Finding Nutrition Studies on Tachycardia The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “tachycardia” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

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Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

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The following information is typical of that found when using the “Full IBIDS Database” to search for “tachycardia” (or a synonym): •

Adenosine is worth trying in patients with paroxysmal supraventricular tachycardia on chronic theophylline medication. Author(s): Universitat Dusseldorf, Abteilung fur Hamatologie, Onkologie und klinische Immunologie, MNR- Klinik, Moorenstr. 5, D-40225 Dusseldorf, Germany. [email protected] Source: Giagounidis, A A Schafer, S Klein, R M Aul, C Strauer, B E Eur-J-Med-Res. 1998 August 18; 3(8): 380-2 0949-2321

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Adenosine-5'-triphosphate-induced sinus tachycardia mediated by prostaglandin synthesis via phospholipase C in the rabbit heart. Author(s): 2nd Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan. Source: Takikawa, R Kurachi, Y Mashima, S Sugimoto, T Pflugers-Arch. 1990 September; 417(1): 13-20 0031-6768

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Bidirectional tachycardia induced by herbal aconite poisoning. Author(s): Department of Medicine, University of Hong Kong. Source: Tai, Y T Lau, C P But, P P Fong, P C Li, J P Pacing-Clin-Electrophysiol. 1992 May; 15(5): 831-9 0147-8389

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Bromocriptine-induced tachycardia in conscious rats: blunted response following isoproterenol pretreatment for 5 days. Author(s): Departamento de Fisiologia e Farmacologia, Centro de Ciencias Biologicas, Universidade Federal de Pernambuco, Recife-PE, Brasil. Source: Lahlou, S Duarte, G P Acta-Physiol-Pharmacol-Ther-Latinoam. 1998; 48(3): 16574 0327-6309

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Cycle length alternation during supraventricular tachycardia: occurrence and mechanism in a canine model of AV reentrant tachycardia. Author(s): Department of Medicine, University of Montreal, Quebec, Canada. Source: Talajic, M Villemaire, C Papadatos, D Lemery, R Roy, D Nattel, S Pacing-ClinElectrophysiol. 1990 March; 13(3): 314-25 0147-8389

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Differential effects of atropine and isoproterenol on inducibility of atrioventricular nodal reentrant tachycardia. Author(s): Department of Cardiology and Internal Medicine, University of Technology, Aachen, Germany. [email protected] Source: Stellbrink, C Diem, B Schauerte, P Brehmer, K Schuett, H Hanrath, P J-IntervCard-Electrophysiol. 2001 December; 5(4): 463-9 1383-875X

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Effects of intravenous disopyramide and quinidine on normal myocardium and on the characteristics of arrhythmias: intraindividual comparison in patients with sustained ventricular tachycardia. Source: Rizos, I Brachmann, J Lengfelder, W Schmitt, C von Olshausen, K Kubler, W Senges, J Eur-Heart-J. 1987 February; 8(2): 154-63 0195-668X

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Effects of pharmacological autonomic blockade on dual atrioventricular nodal pathways physiology in patients with slow-fast atrioventricular nodal reentrant tachycardia. Author(s): Department of Internal Medicine, National Cheng-Kung University Hospital, Tainan, Republic of China. Source: Lin, L J Lin, J L Lai, L P Chen, J H Tseng, Y Z Lien, W P Pacing-ClinElectrophysiol. 1998 July; 21(7): 1375-9 0147-8389

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Generating and influencing Torsades de Pointes--like polymorphic ventricular tachycardia in isolated guinea pig hearts. Author(s): Department of Veterinary Pharmacology, Bern, Switzerland. Source: Gerhardy, A Scholtysik, G Schaad, A Haltiner, R Hess, T Basic-Res-Cardiol. 1998 August; 93(4): 285-94 0300-8428

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Magnesium deficiency in adult rats promotes the induction of ventricular tachycardia by the administration of epinephrine. Author(s): The Graduate School of Health and Nutrition Sciences, Nakamura-Gakuen University, Fukuoka, Japan. Source: Tomiyasu, T Chishaki, A Nakamura, M Heart-Vessels. 1998; 13(3): 122-31 09108327

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Multifocal atrial tachycardia as a prognostic indicator in patients with severe chronic obstructive pulmonary disease requiring mechanical ventilation. Author(s): Department of Chest Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan, R.O.C. Source: Tsai, Y H Lee, C J Lan, R S Lee, C H Changgeng-Yi-Xue-Za-Zhi. 1991 September; 14(3): 163-7

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Polymorphic ventricular tachycardia in a woman taking cesium chloride. Author(s): Section of Cardiac Electrophysiology and Pacing, Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195, USA. [email protected] Source: Saliba, W Erdogan, O Niebauer, M Pacing-Clin-Electrophysiol. 2001 April; 24(4 Pt 1): 515-7 0147-8389

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Polymorphous ventricular tachycardia as undesirable effect of the association of quinidine treatment with hysteresis ventricular inhibited pacing. Author(s): Istituto di Cardiologia, University of Milan, Italy. Source: Della Bella, P Tondo, C Marenzi, G Grazi, S Eur-Heart-J. 1990 December; 11(12): 1124-6 0195-668X

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Postoperative junctional ectopic tachycardia. Author(s): Department of Anesthesiology, Saint Louis University Medical Center, MO 63110, USA. Source: Azzam, F J Fiore, A C Can-J-Anaesth. 1998 September; 45(9): 898-902 0832-610X

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Sheehan's syndrome with hypomagnesemia and polymorphous ventricular tachycardia. Author(s): Second Department of Internal Medicine, School of Medicine, Kanazawa University, Ishikawa, Japan. Source: Nunoda, S Ueda, K Kameda, S Nakabayashi, H Jpn-Heart-J. 1989 March; 30(2): 251-6 0021-4868

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Slow ventricular tachycardia located in the epicardium of the left ventricular base and characterized by effects of adenosine triphosphate, nicorandil and verapamil. Author(s): Third Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan. Source: Kobayashi, Y Miyata, A Tanno, K Kikushima, S Baba, T Katagiri, T Jpn-Circ-J. 1998 December; 62(12): 947-51 0047-1828

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Sotalol associated torsades de pointes tachycardia in a 15-month-old child: successful therapy with magnesium aspartate. Author(s): Department of Paediatrics III, Children's Hospital, University School of Medicine Hannover, Germany.

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Source: Sasse, M Paul, T Bergmann, P Kallfelz, H C Pacing-Clin-Electrophysiol. 1998 May; 21(5): 1164-6 0147-8389 •

Spontaneous sustained monomorphic ventricular tachycardia after administration of ajmaline in a patient with Brugada syndrome. Author(s): Department of Cardiology, University Hospital Virgen de la Arrixaca, Murcia, Spain. Source: Pinar Bermudez, E Garcia Alberola, A Martinez Sanchez, J Sanchez Munoz, J J Valdes Chavarri, M Pacing-Clin-Electrophysiol. 2000 Mar; 23(3): 407-9 0147-8389

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Swallowing-induced tachycardia: electrophysiologic and pharmacologic observations. Author(s): Cardiac Electrophysiology Laboratory, Thomas Jefferson University Hospital, Philadelphia, PA 19107. Source: Greenspon, A J Volosin, K J Pacing-Clin-Electrophysiol. 1988 November; 11(11 Pt 1): 1566-70 0147-8389

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Termination of paroxysmal supraventricular tachycardia with oral diltiazem. Author(s): Johnson County Internal Medicine Associates, Inc., Franklin, IN 46131-2190. Source: Pauszek, M E Indiana-Med. 1991 May; 84(5): 318-20 0746-8288

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The tachycardia-induced dog model of atrial fibrillation. clinical relevance and comparison with other models. Author(s): Department of Pharmacology, Centre for Therapeutic Research, Merck Frosst Canada, 16711 Trans Canada Hwy., Kirkland, Quebec, Canada. [email protected] Source: Gaspo, R J-Pharmacol-Toxicol-Methods. 1999 September; 42(1): 11-20 1056-8719

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Three types of atrioventricular reciprocating tachycardia using bilateral accessory pathways in a patient with Wolff-Parkinson-White syndrome. Author(s): Division of Cardiology, Tri-Service General Hospital, National Defense Medical Center, Taiwan, Republic of China. Source: Liu, P H Wang, W B Wang, D J Shieh, S M Sung, P K J-Electrocardiol. 1989 April; 22(2): 173-80 0022-0736

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Ventricular tachycardia in a patient with primary hyperparathyroidism. Author(s): Department of Medicine, National Yang-Ming University, School of Medicine, Taipei, Taiwan. Source: Chang, C J Chen, S A Tai, C T Yu, W C Chen, Y J Tsai, C F Hsieh, M H Ding, Y A Chang, M S Pacing-Clin-Electrophysiol. 2000 April; 23(4 Pt 1): 534-7 0147-8389

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

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Google: http://directory.google.com/Top/Health/Nutrition/

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Healthnotes: http://www.healthnotes.com/

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Open Directory Project: http://dmoz.org/Health/Nutrition/

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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

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WebMDHealth: http://my.webmd.com/nutrition

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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CHAPTER 3. ALTERNATIVE MEDICINE AND TACHYCARDIA Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to tachycardia. At the conclusion of this chapter, we will provide additional sources.

National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to tachycardia and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “tachycardia” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to tachycardia: •

Adenosine for the management of patients with tachycardias--a new protocol. Author(s): Domanovits H, Laske H, Stark G, Sterz F, Schmidinger H, Schreiber W, Mullner M, Laggner AN. Source: European Heart Journal. 1994 May; 15(5): 589-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8055996

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Adenosine versus verapamil in the treatment of supraventricular tachycardia: a randomized double-crossover trial. Author(s): Hood MA, Smith WM. Source: American Heart Journal. 1992 June; 123(6): 1543-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1595533

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Adenosine-sensitive ventricular tachycardia: evidence suggesting cyclic AMPmediated triggered activity. Author(s): Lerman BB, Belardinelli L, West GA, Berne RM, DiMarco JP.

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Source: Circulation. 1986 August; 74(2): 270-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3015453 •

Atrial activation sequence during junctional tachycardia induced by thermal stimulation of Koch's triangle in canine blood-perfused atrioventricular node preparation. Author(s): Iwasa A, Motomura S, Sasaki S, Daitoku K, Higuma T, Okumura K. Source: Pacing and Clinical Electrophysiology : Pace. 2002 May; 25(5): 753-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12049365

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Atrioventricular block following thumpversion of ventricular tachycardia. Author(s): Barold SS. Source: Pacing and Clinical Electrophysiology : Pace. 2000 November; 23(11 Pt 1): 17034. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11138312

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Bidirectional tachycardia induced by herbal aconite poisoning. Author(s): Tai YT, Lau CP, But PP, Fong PC, Li JP. Source: Pacing and Clinical Electrophysiology : Pace. 1992 May; 15(5): 831-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1382285

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Bidirectional tachycardia. A sustained form, not related to digitalis intoxication, in an adult without apparent cardiac disease. Author(s): Martini B, Buja GF, Canciani B, Nava A. Source: Japanese Heart Journal. 1988 May; 29(3): 381-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3172482

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Catheter ablation of permanent junctional reciprocating tachycardia with radiofrequency current. Author(s): Gaita F, Haissaguerre M, Giustetto C, Fischer B, Riccardi R, Richiardi E, Scaglione M, Lamberti F, Warin JF. Source: Journal of the American College of Cardiology. 1995 March 1; 25(3): 648-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7860909

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Clinical and electrophysiologic features and role of catheter ablation techniques in adult patients with automatic atrioventricular junctional tachycardia. Author(s): Scheinman MM, Gonzalez RP, Cooper MW, Lesh MD, Lee RJ, Epstein LM. Source: The American Journal of Cardiology. 1994 September 15; 74(6): 565-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8074039

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Clonidine suppresses digitalis-induced ventricular tachycardia in cats. Author(s): Liu RH, Chen SA, Chang MS, Ting TH, Chiang BN, Kuo JS.

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Source: Zhonghua Yi Xue Za Zhi (Taipei). 1990 January; 45(1): 15-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2168235 •

Comparison of treatment of supraventricular tachycardia by Valsalva maneuver and carotid sinus massage. Author(s): Lim SH, Anantharaman V, Teo WS, Goh PP, Tan AT. Source: Annals of Emergency Medicine. 1998 January; 31(1): 30-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9437338

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Complications of chest thump for termination of supraventricular tachycardia in children. Author(s): Muller GI, Ulmer HE, Bauer JA. Source: European Journal of Pediatrics. 1992 January; 151(1): 12-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1728536

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Discordant effects of carotid sinus massage and intravenous adenosine in atypical (fast-slow) atrioventricular nodal reentrant tachycardia. Author(s): Milchak MA, Greenberg ML. Source: Pacing and Clinical Electrophysiology : Pace. 1989 December; 12(12): 1903-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2481288

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Effectiveness and safety of oral verapamil to control exercise-induced tachycardia in patients with atrial fibrillation receiving digitalis. Author(s): Panidis IP, Morganroth J, Baessler C. Source: The American Journal of Cardiology. 1983 December 1; 52(10): 1197-201. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6359848

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Effects of different modes of stimulation on the morphology of the first QRS complex following pacing during digitalis-induced ventricular tachycardia: observations in the conscious dog with chronic complete atrioventricular block. Author(s): Gorgels AP, De Wit B, Beekman HD, Dassen WR, Wellens HJ. Source: Pacing and Clinical Electrophysiology : Pace. 1986 November; 9(6 Pt 1): 842-59. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2432487

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Effects of lignocaine on bidirectional tachycardia and on digitalis-induced atrial tachycardia with block. Author(s): Castellanos A, Ferreiro J, Pefkaros K, Rozanski JJ, Moleiro F, Myerburg RJ. Source: British Heart Journal. 1982 July; 48(1): 27-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7082511

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Effects of Saiko-ka-ryukotsu-borei-to, a Japanese Kampo medicine, on tachycardia and central nervous system stimulation induced by theophylline in rats and mice. Author(s): Sanae F, Hayashi H, Chisaki K, Komatsu Y.

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Source: Japanese Journal of Pharmacology. 1999 March; 79(3): 283-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10230855 •

Fetal supraventricular tachycardia. Review of the literature. Author(s): Bergmans MG, Jonker GJ, Kock HC. Source: Obstetrical & Gynecological Survey. 1985 February; 40(2): 61-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3883257

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Fetal supraventricular tachycardia: in utero therapy with digoxin and quinidine. Author(s): Spinnato JA, Shaver DC, Flinn GS, Sibai BM, Watson DL, Marin-Garcia J. Source: Obstetrics and Gynecology. 1984 November; 64(5): 730-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6493666

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First-line management of paroxysmal supraventricular tachycardia. Author(s): Taylor DM, Auble TF, Yealy DM. Source: The American Journal of Emergency Medicine. 1999 March; 17(2): 214-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10102337

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High serum albuterol levels and tachycardia in adult asthmatics treated with highdose continuously aerosolized albuterol. Author(s): Lin RY, Smith AJ, Hergenroeder P. Source: Chest. 1993 January; 103(1): 221-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8417883

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Intra-uterine tachycardia associated with multicystic encephalomalacia (MCE). Author(s): van Doornik MC, Cats BP, Barth PG, van Bodegom F, Moulaert AJ. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 1985 September; 20(3): 191-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4054415

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Intravenous tetrandrine in terminating acute episodes of paroxysmal supraventricular tachycardia. Author(s): Dai GZ, Zeng B, Zhang YL, Lu YX. Source: Chinese Medical Journal. 1990 June; 103(6): 460-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2119958

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Life-threatening ventricular tachycardia due to liquorice-induced hypokalaemia. Author(s): Eriksson JW, Carlberg B, Hillorn V. Source: Journal of Internal Medicine. 1999 March; 245(3): 307-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10205594

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Management of paroxysmal supraventricular tachycardia. Author(s): Ornato JP. Source: Circulation. 1986 December; 74(6 Pt 2): Iv108-10. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3536156

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Modification of ventricular tachycardia by carotid sinus massage. Author(s): Kappos KG, Koulizakis NG, Toutouzas PK. Source: Journal of Electrocardiology. 1996 October; 29(4): 327-32. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8913907

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Multifocal atrial tachycardia as a prognostic indicator in patients with severe chronic obstructive pulmonary disease requiring mechanical ventilation. Author(s): Tsai YH, Lee CJ, Lan RS, Lee CH. Source: Changgeng Yi Xue Za Zhi. 1991 September; 14(3): 163-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1933624

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Non-pharmacological termination of a supraventricular tachycardia. Author(s): Bhagat K. Source: Cent Afr J Med. 1999 September; 45(9): 246-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11019475

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Non-sustained ventricular tachycardia during carotid massage. Author(s): Bohm A, Pinter A, Preda I. Source: Heart (British Cardiac Society). 2001 July; 86(1): 6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11410549

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Out-of-hospital pleomorphic ventricular tachycardia and resuscitation: association with acute myocardial ischemia and infarction. Author(s): White RD, Wood DL. Source: Annals of Emergency Medicine. 1992 October; 21(10): 1282-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1416316

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Pacemaker related tachycardias. Author(s): Den Dulk K, Lindemans FW, Bar FW, Wellens HJ. Source: Pacing and Clinical Electrophysiology : Pace. 1982 July; 5(4): 476-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6180385

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Paclitaxel (Taxol)-associated junctional tachycardia. Author(s): Faivre S, Goldwasser F, Soulie P, Misset JL. Source: Anti-Cancer Drugs. 1997 August; 8(7): 714-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9311449

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Paroxysmal supraventricular tachycardia during treatment with cisplatin and etoposide combination. Author(s): Fassio T, Canobbio L, Gasparini G, Villani F. Source: Oncology. 1986; 43(4): 219-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3725284

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Paroxysmal supraventricular tachycardia in children: clinical features and response to treatment. (A report from Yogyakarta, Indonesia). Author(s): Wahab AS. Source: Paediatr Indones. 1986 July-August; 26(7-8): 127-36. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3774340

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Pharmacologic treatment of supraventricular tachycardia: the German experience. Author(s): Luderitz B, Manz M. Source: The American Journal of Cardiology. 1992 August 20; 70(5): 66A-73A; Discussion 73A-74A. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1510002

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Polymorphic ventricular tachycardia in a woman taking cesium chloride. Author(s): Saliba W, Erdogan O, Niebauer M. Source: Pacing and Clinical Electrophysiology : Pace. 2001 April; 24(4 Pt 1): 515-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11341093

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Polymorphous ventricular tachycardia associated with normal and long Q-T intervals. Author(s): Soffer J, Dreifus LS, Michelson EL. Source: The American Journal of Cardiology. 1982 June; 49(8): 2021-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7081082

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Postoperative junctional ectopic tachycardia. Author(s): Azzam FJ, Fiore AC. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 1998 September; 45(9): 898-902. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9818116

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Probability of supraventricular tachycardia recurrence in pediatric patients. Author(s): Wu MH, Chang YC, Lin JL, Young ML, Wang JK, Lue HC. Source: Cardiology. 1994; 85(5): 284-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7850817

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Relative efficacy of various physical manoeuvres in the termination of junctional tachycardia. Author(s): Mehta D, Wafa S, Ward DE, Camm AJ.

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Source: Lancet. 1988 May 28; 1(8596): 1181-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2897005 •

Spontaneous termination of paroxysmal supraventricular tachycardia following disappearance of bundle branch block ipsilateral to a concealed atrioventricular accessory pathway: the role of autonomic tone in tachycardia diagnosis. Author(s): Waxman MB, Cupps CL. Source: Pacing and Clinical Electrophysiology : Pace. 1986 January; 9(1 Pt 1): 26-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2419852

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Supraventricular tachycardia and pre-excitation syndromes: pharmacological therapy. Author(s): Manz M, Luderitz B. Source: European Heart Journal. 1993 September; 14 Suppl E: 91-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8223763

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Supraventricular tachycardia associated with postpartum metoclopramide administration. Author(s): Bevacqua BK. Source: Anesthesiology. 1988 January; 68(1): 124-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3337365

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Supraventricular tachycardia emergencies: diagnosis and management. Author(s): Del Negro AA, Fletcher RD. Source: Cardiovasc Clin. 1986; 16(3): 101-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3756965

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Sustained symptomatic sinus node reentrant tachycardia: incidence, clinical significance, electrophysiologic observations and the effects of antiarrhythmic agents. Author(s): Gomes JA, Hariman RJ, Kang PS, Chowdry IH. Source: Journal of the American College of Cardiology. 1985 January; 5(1): 45-57. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3964808

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Termination of magnet-unresponsive pacemaker endless loop tachycardia by carotid sinus massage. Author(s): Friart A. Source: The American Journal of Medicine. 1989 July; 87(1): 1-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2741967

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Termination of paroxysmal supraventricular tachycardia by digital rectal massage. Author(s): Roberge R, Anderson E, MacMath T, Rudoff J, Luten R.

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Source: Annals of Emergency Medicine. 1987 November; 16(11): 1291-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3662193 •

Termination of ventricular tachycardia by carotid sinus massage. Author(s): Stern EH, Schweitzer P. Source: Chest. 1983 March; 83(3): 564-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6825491

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Termination of ventricular tachycardia by carotid sinus massage. Author(s): Hess DS, Hanlon T, Scheinman M, Budge R, Desai J. Source: Circulation. 1982 March; 65(3): 627-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7055883

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Termination of ventricular tachycardia by carotid sinus stimulation. Author(s): Grubb BP. Source: International Journal of Cardiology. 1989 June; 23(3): 397-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2737783

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Treatment of paroxysmal supraventricular tachycardia in infancy with digitalis, adenosine-5'-triphosphate, and verapamil: a comparative study. Author(s): Greco R, Musto B, Arienzo V, Alborino A, Garofalo S, Marsico F. Source: Circulation. 1982 September; 66(3): 504-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7201361

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Treatment of paroxysmal supraventricular tachycardia in the emergency department by clinical decision analysis. Author(s): Ornato JP, Hallagan LF, Reese WA, Clark RF, Tayal VS, Garnett AR, Gonzalez ER. Source: The American Journal of Emergency Medicine. 1988 November; 6(6): 555-60. Erratum In: Am J Emerg Med 1990 January; 8(1): 85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3052483

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Treatment of sinus tachycardia with heart-rate feedback. Author(s): Janssen K. Source: Journal of Behavioral Medicine. 1983 March; 6(1): 109-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6876152

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Unstable angina with tachycardia: clinical and therapeutic implications. Author(s): Sclarovsky S, Bassevich R, Strasberg, Klainman E, Rechavia E, Sagie A, Agmon J.

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Source: American Heart Journal. 1988 November; 116(5 Pt 1): 1188-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3189136 •

Using the right drug: a treatment algorithm for regular supraventricular tachycardias. Author(s): Levy S, Ricard P. Source: European Heart Journal. 1997 May; 18 Suppl C: C27-32. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9152672

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Ventricular tachycardia as a complication of digital rectal massage. Author(s): Lieberman ME. Source: Annals of Emergency Medicine.

Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

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Chinese Medicine: http://www.newcenturynutrition.com/

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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html

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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

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Google: http://directory.google.com/Top/Health/Alternative/

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Healthnotes: http://www.healthnotes.com/

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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

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Open Directory Project: http://dmoz.org/Health/Alternative/

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HealthGate: http://www.tnp.com/

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WebMDHealth: http://my.webmd.com/drugs_and_herbs

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/

The following is a specific Web list relating to tachycardia; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

General Overview Angina Source: Integrative Medicine Communications; www.drkoop.com

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Anxiety Source: Integrative Medicine Communications; www.drkoop.com Endocarditis Source: Integrative Medicine Communications; www.drkoop.com Pancreatitis Source: Integrative Medicine Communications; www.drkoop.com •

Herbs and Supplements Adenosine Monophosphate Source: Healthnotes, Inc.; www.healthnotes.com Cactus Grandiflorus Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Ephedra Source: Prima Communications, Inc.www.personalhealthzone.com Glycyrrhiza Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Hawthorn Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Hydrastis Alternative names: Goldenseal; Hydrastis canadensis L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Ma huang Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Mistletoe Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10109,00.html Motherwort Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Passiflora Incarnata Source: Integrative Medicine Communications; www.drkoop.com Passion Flower Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca

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Passionflower Alternative names: Passiflora incarnata Source: Integrative Medicine Communications; www.drkoop.com Sotalol Source: Healthnotes, Inc.; www.healthnotes.com

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.

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CHAPTER 4. DISSERTATIONS ON TACHYCARDIA Overview In this chapter, we will give you a bibliography on recent dissertations relating to tachycardia. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “tachycardia” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on tachycardia, we have not necessarily excluded nonmedical dissertations in this bibliography.

Dissertations on Tachycardia ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to tachycardia. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •

Atrioventricular conduction in patients with paroxysmal supraventricular tachycardias by Liu, Shaowen; PhD from Lunds Universitet (Sweden), 2003, 162 pages http://wwwlib.umi.com/dissertations/fullcit/f371041

Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.

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CHAPTER 5. PATENTS ON TACHYCARDIA Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.8 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “tachycardia” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on tachycardia, we have not necessarily excluded nonmedical patents in this bibliography.

Patents on Tachycardia By performing a patent search focusing on tachycardia, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 8Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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example of the type of information that you can expect to obtain from a patent search on tachycardia: •

Active implantable medical device, in particular a pacemaker, defibrillator and/or cardiovertor of the multisite type, capable of detecting induced tachycardia Inventor(s): Ripart; Alain (Gif sur Yvette, FR) Assignee(s): Ela Medical S.a. (montrouge, Fr) Patent Number: 6,625,491 Date filed: December 1, 2000 Abstract: An active implantable medical device, in particular a pacemaker, defibrillator and/or cardiovertor of the multisite type, capable of detecting an induced tachycardia. Such a device is to be coupled to electrodes placed in at least two cardiac sites of the same cardiac chamber type, e.g., at least two ventricular sites, right and left, at least two atrial sites, right and left, or at least two sites of the same cavity (atria or ventricular). The device has a cardiac signal collection circuit to detect a depolarization potential, and a stimulation circuit to apply stimulation pulses to at least certain of the aforesaid sites. The device monitors the heart rate, detects suspicion of an induced tachycardia condition, operating in response to the heart rate and determines the presence of an induced tachycardia condition if the heart rate exceeds a predetermined threshold for a length of time greater than a predetermined threshold, and temporarily modifies the operation of the device in the event of the detection of an induced tachycardia condition to cause the induced tachycardia condition to disappear. Excerpt(s): The present invention relates to "active implantable medical devices" as such devices are defined by the Jun. 20, 1990 directive 90/385/CEE of the Council of the European Communities, more particularly to pacemaker, defibrillator and/or cardiovertor devices which are able to deliver to the heart stimulation pulses of low energy for the treatment of cardiac rate disorders, and even more particularly to the socalled "multisite" prostheses, in which electrodes are placed in a plurality of distinct respective sites in the tissue. Multisite prosthesis typically comprise at least one ventricular site and one atrial site, and are known as "double chamber" (right atrial stimulation and right ventricular stimulation) or, more generally, "triple chamber" (right atrial stimulation and double ventricular stimulation) or "quadruple chamber" (double atrial stimulation and double ventricular stimulation) prosthesis. Multisite devices also include a prosthesis type which provides stimulation at two distinct sites in the same cavity, for example, a double stimulation of the left ventricle. In addition to the treatment of cardiac rate disorders, it has been proposed to treat by stimulation disorders of the myocardial contraction, which are observed among patients having a cardiac insufficiency. These disorders may be spontaneous or induced by a traditional stimulation. One will be able in particular to refer to the study of J. C. Daubert et al., Stimucoeur, 25, n.degree.3, pp. 170-176 which gives a report on this subject. Daubert et al. proposed to stimulate simultaneously and permanently the left and right ventricles, for the re-synchronization of both ventricles. One often can observe spectacular results for patients having a Class III-type cardiac insufficiency, whose condition was not significantly, if at all, improved by the traditional treatments. Web site: http://www.delphion.com/details?pn=US06625491__

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Apparatus and method for electrical stimulation adjunct (add-on) therapy of atrial fibrillation, inappropriate sinus tachycardia, and refractory hypertension with an external stimulator Inventor(s): Boveja; Birinder R. (P.O. Box 210095, Milwaukee, WI 53221) Assignee(s): None Reported Patent Number: 6,668,191 Date filed: April 19, 2001 Abstract: A system and method of neuromodulation adjunct (add-on) therapy for atrial fibrillation, refractory hypertension, and inappropriate sinus tachycardia comprises an implantable lead-receiver and an external stimulator. Neuromodulation is performed using pulsed electrical stimulation. The external stimulator contains a power source, controlling circuitry, a primary coil, and predetermined programs. The primary coil of the external stimulator inductively transfers electrical signals to the implanted leadreceiver, which is also in electrical contact with a vagus nerve. The external stimulator emits electrical pulses to stimulate the vagus nerve according to a predetermined program. In a second mode of operation, an operator may manually override the predetermined sequence of stimulation. The external stimulator may also be equipped with a telecommunications module to control the predetermined programs remotely. Excerpt(s): This invention relates generally to medical device system for therapy of cardiovascular disorders, more specifically to adjunct (add-on) treatment of certain cardiovascular disorders by neuromodulation of a selected nerve or nerve bundle, utilizing an implanted lead-receiver and an external stimulator. Electrical stimulation of the vagus nerve, and the profound effects of electrical stimulation of the vagus nerve on the central nervous system (CNS) activity extends back to the 1930's. Medical research has furthered our understanding of the role of nervous control of body functions. In the human body there are two vagal nerves (VN), the right VN and the left VN. The innervation of the right and left vagus nerves is different. The innervation of the right vagus nerve is predominately to the sinus (SA) node of the heart, and its stimulation results in slowing of the sinus rate. The cardiac innervation of the left vagus nerve is predominately to the AV node, and its stimulation results in delaying the conduction through the atrioventricular (AV) node. The system and method of the current invention utilizes an implanted lead-receiver, and an external stimulator for adjunct (add-on) treatment or alleviation of symptoms for certain cardiovascular disorders, such as atrial fibrillation, inappropriate sinus tachycardia, and refractory hypertension. The system of this invention delivers neuromodulation pulses according to a limited number of predetermined programs, which are stored in the external stimulator, and can be activated by pressing a button. The predetermined programs contain unique combinations of pulse amplitude, pulse width, frequency of pulses, on-time and offtime. In one embodiment, the system contains a telecommunications module within the external stimulator. In such an embodiment, the external stimulator can be controlled remotely, via wireless communication. Web site: http://www.delphion.com/details?pn=US06668191__

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Apparatus and method for predicting ablation depth Inventor(s): He; Ding Sheng (Tucson, AZ), Taylor; Junius E. (Phoenix, AZ) Assignee(s): Engineering & Research Associates, Inc. (tucson, Az) Patent Number: 6,322,558 Date filed: October 1, 1999 Abstract: During an ablation procedure in a chamber of the heart RF energy is used to form a myocardial lesion for treatment of some arrhythmias such as sustained supraventricular tachycardia and accessory pathways. A galvanic cell formed by a metallic electrode having a first work function at the ablation site, a second metallic electrode having a second work function located remote from the ablation site and the intervening tissue serving as an electrolyte, produces an output current signal reflective of the formation of a lesion at the ablation site and is used to control the RF energy applied. A curve depicting the output current signal has a maximum value at the point a burn or lesion formation and thereafter decreases in value. A short duration inflection or bump of the curve occurs prior to charring and carbonization of the lesion. A further curve representative of the impedance of the tissue between the electrodes is displayed; it shows a rapid impedance rise upon occurrence of carbonization and charring of the tissue. The impedance rise occurs after the bump of the output current signal occurs. By terminating application of RF power after occurrence of the bump, and before impedance rise charring of the tissue and other negative results will not occur. A physician can use the bump and the impedance rise as limit indicators for determining lesion formation of a predictable depth without incurring unwanted damage. Excerpt(s): The present invention relates to apparatus and methodology for ablating tissue and, more particularly, to determination of an unambiguous formation of a lesion having a predictable depth and volume at an ablation site. The heart is a four chamber muscular organ (myocardium) that pumps blood through various conduits to and from all parts of the body. In order that the blood be moved in the cardiovascular system in an orderly manner, it is necessary that the heart muscles contract and relax in an orderly sequence and that the valves of the system open and close at proper times during the cycle. Specialized conduction pathways convey electrical impulses swiftly to the entire cardiac muscle. In response to the impulses, the muscle contracts first at the top of the heart and follows thereafter to the bottom of the heart. As contraction begins, oxygen depleted venous blood is squeezed out of the right atrium (one of two small upper chambers) and into the larger right ventricle below. The right ventricle ejects the blood into the pulmonary circulation, which resupplies oxygen and delivers the blood to the left side of the heart. In parallel with the events on the right side, the heart muscle pumps newly oxygenated blood from the left atrium into the left ventricle and from there out to the aorta which distributes the blood to every part of the body. The signals giving rise to these machinations emanates from a cluster of conduction tissue cells collectively known as the sinoatrial (SA) node. The sinoatrial node, located at the top of the atrium, establishes the tempo of the heartbeat. Hence, it is often referred to as the cardiac pacemaker. It sets the tempo simply because it issues impulses more frequently than do other cardiac regions. Although the sinoatrial node can respond to signals from outside the heart, it usually becomes active spontaneously. From the sinoatrial node impulses race to the atrioventricular (AV) node above the ventricles and speeds along the septum to the bottom of the heart and up along its sides. The impulses also migrate from conduction fibers across the overlying muscle from the endocardium to the epicardium to trigger contractions that force blood through the heart and into the arterial circulation. The spread of electricity through a healthy heart gives rise to the

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familiar electrocardiogram. Defective or diseased cells are electrically abnormal. That is, they may conduct impulses unusually slowly or fire when they would typically be silent. These diseased cells or areas might perturb smooth signaling by forming a reentrant circuit in the muscle. Such a circuit is a pathway of electrical conduction through which impulses can cycle repeatedly without dying out. The resulting impulses can provoke sustained ventricular tachycardia: excessively rapid pumping by the ventricles. Tachycardia dysrhythmnia may impose substantial risk to a patient because a diseased heart cannot usually tolerate rapid rates for extensive periods. Such rapid rates may cause hypotension and heart failure. Where there is an underlying cardiac disease, tachycardia can degenerate into a more serious ventricular dysrhythmia, such as fibrillation. By eliminating a reentrant circuit or signal pathway contributing to tachycardia, the source of errant electrical impulses will be eliminated. Ablation of the site attendant such a pathway will eliminate the source of errant impulses and the resulting arrhythmia. Mapping techniques for locating each of such sites that may be present are well known and are presently used. Interruption of the errant electrical impulses is generally achieved by ablating the appropriate site. Such ablation has been performed by lasers. The most common technique used at an ablation site involves the use of a probe energized by radio frequency (RF) radiation. Radio frequency (RF) catheter ablation is an effective therapy for the treatment of sustained supraventricular tachycardias such as that due to an accessory pathway. (Jackman, et al. "Catheter ablation of accessory AV pathways (Wolff-Parkinson-White Syndrome) by radiofrequency current", N. Engl J. Med 1991;324:1605-1611; Calkins, et al. "Diagnosis and cure of the Wolff-Parkinson-White syndrome or paroxysmal supraventricular tachycardias during a single electrophysiology test", N. Engl J. Med 1991;324:1612-1618; Kuck et al.;"Radiofrequency current catheter ablation of accessory atrioventricular pathways", Lancet 1991;337:1557-1561; Lesh et al., "Curative percutaneous catheter ablation using radiofrequency energy for accessory pathways in all locations; Results in 100 consecutive patients", J. Am. Coll Cardiol 1992;19:1303-1309; Lee et al., "Catheter modification of the atrioventricular junction with radiofrequency energy for control of atrioventricular nodal reentry tachycardia", Circulation 1991;83:827-835; Jackman et al., "Treatment of supraventricular tachycardia due to atrioventricular nodal reentry by radiofrequency catheter ablation of slow pathway conduction", N.Eng J. Med 1992;327:313-318; Kay et al., "Selective radiofrequency ablation of the slow pathway for the treatment of atrioventricular nodal reentrant tachycardia. Evidence for involvement of perinodal myocardium within the reentrant circuit", Circular. 1992,85(5):1675-88; Jazayeri et al., "Selective transcatheter ablation of the fast and slow pathways using radiofrequency energy in patients with atrioventricular nodal reentry tachycardia", Circulation 1992;85:1318-1328; Klein et al., "Radiofrequency catheter ablation of ventricular tachycardia in patients without structural heart disease", Circulation 1992;85:1666-6174; Nakagawa et al., "Radiofrequency catheter ablation of idiopathic left ventricular tachycardia guided by a Purkinje potential", Circulation 1993;88:2607-2617.) The treatment of atrial fibrillation and ventricular tachycardia by catheter ablation requires longer or deeper lesions. If lesion formation below an electrode could be accurately monitored during its formation, it could improve the ability to produce a continuous line of lesions that is required for ablation of atrial fibrillation. Also, creating deeper lesions could enhance the success of ablation of ventricular tachycardia. Web site: http://www.delphion.com/details?pn=US06322558__

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Battery conservation in implantable cardioverter-defibrillators and pacemakers Inventor(s): Causey, III; James D. (Simi Valley, CA), Mouchawar; Gabriel (Newhall, CA) Assignee(s): Pacesetter, Inc. (sylmar, Ca) Patent Number: 6,363,280 Date filed: October 15, 1999 Abstract: In an implantable cardioverter-defibrillator and/or pacemaker, each having DDD pacing capabilities, an improved method of operation is described which dramatically increases the longevity of the implanted device by conserving battery power. The method comprises deactivating at least one unnecessary, power-consuming feature of the device until such feature is needed and then reactivating said feature only for so long as it is required by the patient. In a particular embodiment, the atrial sense amplifier is deactivated during normal operation of the implantable device, resulting in single-chamber sensing and pacing. Upon the occurrence of a predefined event, indicative of a need for dual-chamber sensing and pacing, the atrial sense amplifier is reactivated, the need for DDD pacing confirmed, and if appropriate, DDD pacing is begun. Once the patient's heart rate has returned to an acceptable level, the atrial sense amplifier is again deactivated and single-chamber sensing/pacing continued. In addition, the atrial sense amplifier of an ICD/pacemaker is deactivated during normal operation of the device and reactivated immediately following the detection of ventricular tachycardia. In this embodiment, DDD sensing/pacing is preferably automatically begun following this detection. Also contemplated herein, are improved devices employing the improved methods. Excerpt(s): The subject matter disclosed and claimed herein relates to an improved method of operation of pacemakers and implantable cardioverter-defibrillators (ICDs) having pacing capabilities, which improved method serves to prolong battery longevity by deactivating certain power-consuming features while not needed and reactivating as necessary. Also provided herein are improved devices employing these methods. The heart functions to pump life-sustaining blood throughout one's body. The human heart comprises a left side and a right side with each side having a first chamber known as the atrium and a second chamber known as the ventricle. The right atrium receives blood from the body after the body has extracted the oxygen therefrom and the left atrium receives oxygenated blood from the lungs. At an appropriate time, an electrical stimulus is provided to the atria that causes the muscle tissue to depolarize. Immediately following depolarization, the atrial muscle tissue physically contracts, forcing the blood held in the right and left atria through one-way valves into the right and left ventricles, respectively. The electrical stimulus provided to the atria also stimulates the ventricles after a delay which is sometimes referred to as the "natural conduction time" of the heart. Upon stimulation, the ventricular muscle tissue depolarizes and then contracts. This forces the blood held within the right ventricle to pass through the pulmonary artery to the lungs and the blood held within the left ventricle to pass through the aorta to the rest of the body. In this manner, then, the heart "beats" or pumps blood by having the atria contract and, after the natural conduction time, by having the ventricles contract. After a longer delay, during which delay the right atrium is refilled with blood returning from throughout the body, the process repeats. Web site: http://www.delphion.com/details?pn=US06363280__

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Cardiac arrhythmia detector using ECG waveform-factor and its irregularity Inventor(s): Lin; Dongping (Irvine, CA), Zhang; Xu-Sheng (Santa Ana Heights, CA) Assignee(s): Cardiac Science Inc. (irvine, Ca) Patent Number: 6,480,734 Date filed: June 30, 2000 Abstract: A cardiac monitor is provided that monitors the condition of the heart of a cardiac patient and generates signals indicating one of several conditions, such as supraventricular tachycardia, ventricular tachycardia and ventricular fibrillation. In order to generate these signals, the ECG from the patient is analyzed to determine a cardiac interval and heart rate, as well as a waveform factor and a waveform factor irregularity. The waveform factor is derived from the average of the ECG amplitudes during a cardiac interval and the peak value of the ECG during the same interval. Preferably, a running average is calculated over several intervals. This waveform factor is then used to detect shockable ventricular arrhythmia. The waveform factor irregularity is indicative of the variability of the waveform factor and is used to differentiate between ventricular tachycardia and ventricular defibrillation. Excerpt(s): The present invention relates generally to a cardiac arrhythmia detector in a prosthesis such as an internal or external cardiac defibrillator and pacemaker. More specifically, such a detector comprises a microprocessor used to perform an arrhythmia detection algorithm that detects and analyzes an ECG waveform factor and its irregularity for promptly and accurately discriminating among various types of cardiac arrhythmias, including ventricular fibrillation (VF), ventricular tachycardia (VT), supraventricular tachycardia (SVT), or other arrhythmias. Sudden cardiac arrest (SCA) accounts for about 76% of sudden non-traumatic deaths in adults and about 50% of all cardiac deaths. Approximately 350,000 Americans experience SCA each year with only about 5% national survival rate. Even in hospital, the percentage of patients who survive SCA is not encouraging. This percentage has remained stable at approximately 15%, and has not improved in the last 30 years. Thus SCA still represents a major and unresolved public health problem. Ventricular tachyarrhythmia (which includes ventricular fibrillation (VF) and ventricular tachycardia (VT)) is the most common initial incidence of SCA. Unlike other life-threatening conditions such as cancer or AIDS, there is an effective, inexpensive and standard therapy for SCA: timely cardioversion/defibrillation applied by a cardiac stimulator device. Early timely cardioversion/defibrillation (i.e., immediately after onset) is the key to survival, since the chances of success are reduced by 10 percent for every minute of delay of the treatment. Death usually follows unless a normal heart rhythm is restored within 5-7 minutes. Therefore, it is the lack of warning, i.e. detection, and the delay for intervention, not a lack of effective treatment, that accounts for the high death rate following SCA. Web site: http://www.delphion.com/details?pn=US06480734__

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Cardioelectric apparatus Inventor(s): Weiss; Ingo (Erlangen, DE) Assignee(s): Biotronik Mess-und Therapiegerate Gmbh & Co. Ingenieurburo Berlin (berlin, De) Patent Number: 6,466,819 Date filed: June 26, 2000

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Abstract: A cardioelectric apparatus for the early detection of a tachycardia of the heart is provided. The cardioelectric apparatus of the current invention, comprising: 1) measurement means for sensing measurement values for the heart rate and the action potential duration, the measurement means having at least one output for the output of measurement value pairs of mutually associated measurement values for the heart rate and the action potential duration; 2) measurement value processing means for receiving the measurement value pairs, the measurement value processing means connected to the output of the measurement means and which are adapted to derive from the measurement value pairs time-variant parameters (.tau.sub.x, g) which describe the heart; 3) a memory in which comparative values characterizing a tachycardia risk can be stored; and 4) an evaluation unit connected to the measurement value processing means for receiving the parameters (.tau.sub.x, g) derived from the measurement value pairs and further connected to the memory and which is adapted to compare the derived parameters (.tau.sub.x, g) to comparative values stored in the memory and to output a tachycardia risk signal if the comparison of the derived parameters (.tau.sub.x, g) with the comparative values shows that the derived parameters (.tau.sub.x, g) are in the tachycardia risk range. Excerpt(s): The invention concerns an apparatus for early detection of a tachycardia of a heart. The human heart, can go into physiologically disturbing and possibly fatal states. One such state is a tachycardia, which is distinguished by very rapidly succeeding heart beats, that is to say a high heart rate with a simultaneously reduced pumping capacity on the part of the heart. Apparatuses for detecting and treating such tachycardia phenomena, for example cardioverters or defibrillators, are well-known. A disadvantage of the known apparatuses are that they detect a tachycardia situation only when it has already occurred. Web site: http://www.delphion.com/details?pn=US06466819__ •

Determination of pacemaker wenckebach and adjustment of upper rate limit Inventor(s): Conville; Rick P. (Columbia, MD), Stahl; Wyatt K. (Vadnais Heights, MN), Voegele; John M. (East Bethel, MN) Assignee(s): Cardiac Pacemakers, Inc. (st. Paul, Mn) Patent Number: 6,564,095 Date filed: November 27, 2000 Abstract: A method of determining the cause of upper rate limit behavior in a dual chamber pacemaker incorporating a system for distinguishing Wenckebach episodes from pacemaker mediated tachycardia episodes based on variations in VA intervals is disclosed which provides for adjusting the MTR upward in response to a threshold frequency of incidences of Wenckebach. Excerpt(s): The present invention relates generally to the field of cardiac rhythm management and more particularly to a dual chamber cardiac pacemaker incorporating a system for discriminating between pacemaker mediated tachycardia (PMT) and simple upper rate limit Wenckebach behavior due to normal sinus tachycardia. The system may also provide for adjusting the upper rate limit (URL) or maximum tracking rate (MTR) according to the frequency of detected pacemaker Wenckebach events. In dual chamber pacemakers, circuitry is provided for both sensing atrial and ventricular depolarization events and for pacing one or both of atrial and ventricular tissue. In a subject with normal sinus node activity and interrupted conduction system, the

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pacemaker is able to sense an atrial depolarization (P-wave) and thereafter stimulate the ventricle in accordance with an established AV delay interval. This effectively mimics the heart's PR interval. The situation is complicated, however, by the possible occasional occurrence of an interfering retrograde conducted P-wave, possibly the result of a ventricular stimulating pulse, but one which is also sensed by the atrial sensing circuitry. Because the atrial sensing circuitry of the pacemaker cannot tell whether a sensed signal is a normal or retrograde conducted P-wave it will initiate another ventricular stimulation event. This may quickly lead to PMT. To overcome this problem, dual chamber pacemakers are typically programmed to include a post-ventricular atrial refractory period (PVARP) during which atrial events are sensed but ignored. In this manner, if an atrial event occurs during PVARP due to retrograde conduction, an AV interval is not initiated and no ventricular stimulating pulse is generated as a result of the atrial event. The addition of PVARP does not totally successfully resolve the problem either, however, because in many pacemaker treated patients the condition of the patient is such that the retrograde conduction time varies or fluctuates depending upon physiologic feedback mechanisms. This means that a fixed, programmable PVARP may become relatively too short over time if retrograde conduction time increases and may no longer serve to inhibit PMT. Conversely, if the PVARP is programmed to be too long, this shortens the sensing window and as the pacing rate reaches the maximum atrial tracking rate or MTR set for the pacemaker, some of the desirable P-waves will fall inside the PVARP and be ignored and this will result in an undesirable drop in the ventricular pacing rate. This is known as a two-to-one block. Thus, each time a P-wave falls within PVARP and an AV block occurs for that cardiac cycle it results in a missing cardiac cycle which is undesirable because it causes short-term loss of AV synchrony and the subsequent loss of cardiac output. Web site: http://www.delphion.com/details?pn=US06564095__ •

Discrimination of supraventricular tachycardia and ventricular tachycardia events Inventor(s): Marcovecchio; Alan F. (Minneapolis, MN) Assignee(s): Cardiac Pacemakers, Inc. (st. Paul, Mn) Patent Number: 6,484,055 Date filed: September 20, 2000 Abstract: A method and system for discrimination of supraventricular tachycardia and ventricular tachycardia events. Morphological features points are extracted from normal sinus rhythm (NSR) complexes and used to generate a NSR template. A numerical convolution is performed using the NSR template and the feature points for each sensed NSR to give a NSR filter output. Using a plurality of NSR complexes, a median NSR filter output template is determined, where the median NSR filter output template has a median value for each value in the NSR filter output. The median NSR filter output template is then used during a tachycardia event to distinguish tachycardia events as either ventricular tachycardia events or supraventricular tachycardia events. Excerpt(s): This invention relates generally to medical devices, and more particularly to a system and method for discriminating supraventricular tachycardia from ventricular tachycardia during a tachycardia event. The heart is generally divided into four chambers, the left and right atrial chambers and the left and right ventricular chambers. As the heart beats, the atrial chambers and the ventricular chambers go through a cardiac cycle. The cardiac cycle consists of one complete sequence of contraction and relaxation of the chambers of the heart. The terms systole and diastole are used to

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describe the contraction and relaxation phases the chambers of the heart experience during a cardiac cycle. In systole, the ventricular muscle cells contract to pump blood through the circulatory system. During diastole, the ventricular muscle cells relax, causing blood from the atrial chamber to fill the ventricular chamber. After the period of diastolic filling, the systolic phase of a new cardiac cycle is initiated. Through the cardiac cycle, the heart pumps blood through the circulatory system. Effective pumping of the heart depends upon five basic requirements. First, the contractions of cardiac muscle must occur at regular intervals and be synchronized. Second, the valves separating the chambers of the heart must fully open as blood passes through the chambers. Third, the valves must not leak. Fourth, the contraction of the cardiac muscle must be forceful. Fifth, the ventricles must fill adequately during diastole. Web site: http://www.delphion.com/details?pn=US06484055__ •

Enslaved active implantable medical device protected from the effects of bradyand/or tachy-dependent extrasystoles Inventor(s): Bonnet; Jean-Luc (Montrouge, FR), Bouhour; Anne (Ville d'Avray, FR), Limousin; Marcel (Paris, FR) Assignee(s): Ela Medical S.a. (montrouge, Fr) Patent Number: 6,408,209 Date filed: July 14, 2000 Abstract: A rate-responsive active implantable medical device, in particular a cardiac pacemaker, defibrillator or cardiovertor, which is protected from the effects of bradycardia- and/or tachycardia-dependent extrasystoles. The device is able to stimulate at least one cardiac cavity by delivering low-energy pulses to the heart at a frequency determined by the device, and evaluates the activity level of the patient bearing the device and discriminates between phases of rest, normal activity and effort. Further, the device is capable of adjusting the frequency according to the determined activity level, more particularly decreasing the base frequency to a given minimum level during a rest phase. The device also detects the occurrence of brady-dependent extrasystoles, determines a corresponding extrasystole rate, and then increases the base frequency minimum level when the extrasystole rate exceeds a predetermined threshold during the rest phase. In a similar manner, tachy-dependent extrasystoles are diagnosed and the stimulation rate maximum is adjusted (reduced). These adjustments inhibit the appearance of extrasystoles. Excerpt(s): The present invention relates to "active implantable medical devices" as defined by the Jun. 20, 1990 Directive No. 90/385/CEE of the Council of the European Communities, more particularly to pacemakers, defibrillators and/or cardiovertors which are capable of delivering low-energy stimulation pulses to the heart for treatment of heart (cardiac) rate disorders. The invention also relates to the prevention of consequences which extrasystoles can have on the operation of such devices. Extrasystoles, the appearance of an extra spontaneous contraction of a cardiac chamber out of the normal sequence and rhythm, are known. They can be either ventricular in origin (VES) or atrial in origin (AES). There are two types of VES extrasystoles. The first VES type corresponds to a ventricular detection (i.e., the sensing or "detection" of a spontaneous ventricular contraction) or ventricular stimulation (i.e., a low-energy stimulation pulse delivered by the device in the ventricle) that is not preceded by an atrial event (i.e., either an atrial detection or a stimulation delivered by the device in the atrium) in an interval of time considered to be physiological. A physiological time

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interval refers to the time following an atrial event when a ventricular event should occur to be physiologically healthy to a patient, for example, an interval ranging between 31 and 300 ms. A second VES type corresponds to a ventricular detection that is preceded by an atrial event in an interval of time ranging between 31 and 300 ms, if the atrio-ventricular time (i.e., the time occurring between the atrial event and the following ventricular detection) of the examined cycle is at least 31 ms less than the atrioventricular time of the preceding cardiac cycle. The "cardiac cycle" is defined as the interval of time between two events of a comparable nature in the same cardiac cavity. Web site: http://www.delphion.com/details?pn=US06408209__ •

Implant cardioverter, especially defibrillator Inventor(s): Thong; Tran (Portland, OR) Assignee(s): Biotronik Meb-und Therapiegerate Gmbh & Co. Ingenieurburo Berlin (berlin, De) Patent Number: 6,345,199 Date filed: September 29, 1999 Abstract: An implantable cardioverter, especially defibrillator, having a morphology detector (3) to measure and evaluate EKG signals for the purpose of discriminating between different tachycardia conditions of the heart. The morphology detector (3) having a signal width detector, by which the respective width of the EKG signal between every two successive crossings through the isoelectrical line of the EKG can be measured; a threshold value discriminator to determine whether the EKG signal between two such successive crossings exceeds a defined threshold value; and a comparator for the signal width, coupled to the signal width detector and the threshold value discriminator. The morphology detector compares the respective current signal width value selected by the threshold value discriminator and measures by signal width detector to a pre-set selection parameter to differentiate between two different conditions of tachycardia. Excerpt(s): The present invention relates to an implantable cardioverter, especially a defibrillator, with a morphology detector for detection and evaluation of electrocardiogram (EKG) signals for the purpose of discriminating between different tachycardia conditions of the heart. Regarding the background of the invention, it is important to note in principle, that pathological rhythm abnormalities of the heart, socalled "tachycardias," exist as a clinical picture, which can occur either atrial or ventricular, i.e., in the atrium of the heart or in the ventricle. This is a condition of the heart with a pathologically increased heart rate, which can be significantly higher than 100 beats per minute. In this context one generally distinguishes between two different disorder patterns, i.e., the atrial or ventricular fluttering on one hand and the atrial or ventricular fibrillation on the other hand. The "fluttering" is a rapid succession of relatively regular heart actions, during which a certain pumping capacity of the heart still remains available. During the "fibrillation" on the other hand, an asynchronous action of the heart muscle cells is present, by which an effective pumping action is no longer achieved. Both of the above conditions can have identical rates, however, they can be vastly different in their stability and, therefore, in their consequences for the patient. The two types of disorder, "fluttering" and "fibrillation," therefore, call for different cardiological responses. A modern pacemaker or cardioverter must, therefore, be able to distinguish exactly between conditions of fluttering and conditions of fibrillation, to be able to take the appropriate actions. For this purpose these devices

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incorporate the above-mentioned morphology detector, which detects and evaluates the EKG signal in a suitable manner. Naturally, a large range of options exists for the actual method by which the signals are processed and translated into action, which are limited primarily by the special location and related conditions of compatibility for a cardioverter or defibrillator. Web site: http://www.delphion.com/details?pn=US06345199__ •

Implantable cardioversion device with a self-adjusting threshold for therapy selection Inventor(s): Kroll; Mark W. (Simi Valley, CA) Assignee(s): Pacesetter, Inc. (sylmar, Ca) Patent Number: 6,445,949 Date filed: January 5, 2000 Abstract: In an implantable cardioversion device, the condition of the patient's heart is determined from an intrinsic ventricular parameter, such as the ventricular rate, and therapy is provided with a shock or pulse generator, including, for instance, antitachycardia pacing therapy or defibrillation shocks. Initially, the conditions, i.e., ventricular tachycardia or fibrillation/flutter, are determined using predetermined values for a set of thresholds defining the various conditions. Thereafter, the thresholds are changed by increasing or decreasing the therapy thresholds from the predetermined values based on the success rate of the corresponding therapy. Excerpt(s): This invention pertains to implantable cardioversion devices (ICDs) which sense a dangerous cardiac arrhythmia and, in response, provide therapy to the patient's heart to revert it to a normal sinus rhythm. More particularly, the invention pertains to implantable medical devices and methods, such as an ICD including a sensor for sensing intrinsic cardiac activity and a cardioverter/defibrillator adapted to provide different types of antitachycardia therapy dependent upon the condition of the heart as indicated by the sensor. The ICD is further provided with an automated threshold adjustment means for setting the threshold(s) delimiting the therapies. As used herein, the term "abnormal arrhythmia" refers to any abnormal heart rhythm that may be dangerous to the patient and specifically includes fibrillation, tachycardias, supraventricular tachycardias (SVT), ventricular tachycardias (VT), ventricular fibrillation and flutter (VF), and bradycardia. As further used herein, the term "therapy" refers to any means used by the ICD to restore normal heart rhythm such as defibrillation, cardioversion, antitachycardia pacing (ATP), antibradycardia therapy and drug infusion. The disclosed invention has application to ICDs which treat tachyarrhythmias (abnormally high heart rates). It has been common practice to monitor the heart rate, or more commonly the ventricular rate, of a patient and classify the cardiac condition of the patient based on this heart rate. (Other criteria, in addition to the ventricular rate, may also be used for this classification, but these criteria are omitted for the sake of clarity). For example, tachyarrhythmia may be defined as any rate in a range above a designated threshold VT1. This range is then divided into ventricular tachycardia and ventricular fibrillation (and flutter) zones. The ventricular tachycardia zone may be further divided into slow ventricular tachycardia and fast ventricular tachycardia zones. Web site: http://www.delphion.com/details?pn=US06445949__

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Implantable stimulation device and method for determining atrial autocapture using programmable AV delay Inventor(s): Endaya; Melinda (Granada Hills, CA), Levine; Paul A. (Newhall, CA), Mann; Brian M. (Edgartown, MA) Assignee(s): Pacesetter, Inc. (sylmar, Ca) Patent Number: 6,285,908 Date filed: August 23, 1999 Abstract: A pacemaker programmer and diagnostic system retrieves information stored within a pacemaker and analyzes the retrieved data in real time. The stored information can be retrieved by means of a telemetry communication link. The pacemaker automatically lengthens a post-ventricular atrial refractory period (PVARP). The pacemaker determines atrial capture threshold by generating atrial stimulation pulses while maintaining the ventricular stimulation pulse amplitude at a level known to ensure ventricular capture, and by detecting loss of atrial capture. In response to the loss of atrial capture, a processor automatically shortens the AV delay in a subsequent cardiac cycle, to reduce the possibility of a retrograde P-wave initiating a pacemakermediated tachycardia (PMT). Also in response to the loss of atrial capture, the pacemaker records the atrial capture threshold, restores the PVARP to its pre-test value, and sets the atrial stimulation pulse amplitude to a value above the atrial capture threshold. Excerpt(s): The present invention relates generally to cardiac pacemakers, and other types of implantable medical devices, which can be programmed and/or analyzed following implantation using an external diagnostic/programmer system. More particularly, the invention relates to an implantable dual-chamber pacemaker, including software routines thereof, for automatically determining atrial capture using a programmable AV delay to prevent pacemaker-mediated tachycardia. Implantable cardiac pacemakers commonly store a variety of different types of diagnostic data which assist the physician in evaluating both the operation of the patient's heart and the operation of the implanted device. Depending upon the particular pacemaker and its mode of operation, this information may include, for example, a heart rate histogram (which indicates the distribution of the patient's heart rate over a period of time, such as one month), an event histogram (which indicates the distribution of the various sensing and stimulation events), a sensor indicated rate histogram (which indicates the distribution over time of the recommended pacing rate indicated by an implanted sensor), a variety of event counters, one or more event-triggered intracardiac electrograms, and the status of the pacemaker's battery. The various items of diagnostic data may be retrieved from the pacemaker for display and evaluation using a pacemaker programmer/diagnostic system ("programmer"), which uses RF telemetry to communicate with the implanted device. This is typically accomplished during routine follow-up visits of the patient to the clinic, during which time the patient is asked to hold a telemetry wand in the locality of the implanted pacemaker. To read out and view a particular item of information (e.g., a heart rate histogram), the physician employs a user interface of the programmer to designate the diagnostic item to be retrieved, and then initiates the retrieval. The programmer in-turn interrogates the pacemaker to cause the pacemaker to transmit the selected diagnostic item, and then receives and displays the selected item on the screen. The physician may also initiate various types of tests using the programmer, such as a ventricular or atrial capture test which determines the minimum pulse voltage needed to effectively stimulate the respective chamber of the heart. The physician may retrieve and adjust various programmable pacing parameters,

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such as sensor control parameters that are used to adjust the pacing rate according to the output of an event (or other) sensor which senses electrical activity generated within the cardiac tissue. Web site: http://www.delphion.com/details?pn=US06285908__ •

Method and apparatus diagnosis and treatment of arrhythias Inventor(s): Stadler; Robert W. (Shoreview, MN) Assignee(s): Medtronic, Inc. (minneapolis, Mn) Patent Number: 6,567,691 Date filed: March 22, 2000 Abstract: Adaptive rules for a more accurate sinus tachycardia detection mechanism for implantable device (IMD) and other devices. In an embodiment, the rule is incorporated into a prioritized, rule-based arrhythmia classification system in an IMD. If the rule is met, anti-tachyarrhythmia therapy is withheld even if a lower priority rule determines presence of a treatable tachyarrhythmia. The rule includes adaptive onset criterion, where an expected range of R--R is calculated based on a trimmed mean and a metric of R--R variability derived over a preceding series of R--R intervals. Pattern codes indicative of gradual rate changes and normal sinus rhythm will be within a grammar defined by a continuous recognition machine and will if they persist, result in the ST rule being met. All other codes inconsistent with sinus tachycardia will not adhere to the associatd grammar and will result in the ST rule not being met. Excerpt(s): This invention relates to devices which detect and/or treat tachyarrhythmias (rapid heart rhythms), and more specifically, to mechanisms to distinguish among various tachyarrhythmias and to provide appropriate therapies to treat the identified tachyarrhythmias. Early automatic tachyarrhythmia detection systems for automatic cardioverter/defibrillators relied upon the presence or absence of electrical and mechanical heart activity (such as intra-myocardial pressure, blood pressure, impedance, stroke volume or heart movement) and/or the rate of the electrocardiogram to detect hemodynamically compromising ventricular tachycardia or fibrillation. In some pacemaker/cardioverter/defibrillators presently in commercial distribution or clinical evaluation, fibrillation is generally distinguished from ventricular tachycardia using ventricular rate based criteria, In such devices, it is common to specify the rate or interval ranges that characterize a tachyarrhythmia as opposed to fibrillation. However, some patients may suffer from ventricular tachycardia and ventricular fibrillation that have similar or overlapping rates, making it difficult to distinguish low rate fibrillation from high rate tachycardia. In addition, ventricular fibrillation may display R-R intervals that vary considerably, resulting in intervals that may fall within both the tachycardia and fibrillation rate or interval ranges, or outside both. Similarly, supraventricular arrhythmias may be the cause of high ventricular rates, or may be present during ventricular arrhythmias, further increasing the possibilities of misdiagnosis. Web site: http://www.delphion.com/details?pn=US06567691__

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Method and apparatus for temporarily electrically forcing cardiac output in a tachyarrhythmia patient Inventor(s): Kroll; Kai (Minnetonka, MN), Kroll; Mark W. (Minnetonka, MN) Assignee(s): Galvani, Ltd. (minneapolis, Mn) Patent Number: 6,314,319 Date filed: February 17, 1999 Abstract: An electrical method and apparatus for stimulating cardiac cells causing contraction to force hemodynamic output during fibrillation, hemodynamically compromising tachycardia, or asystole. Forcing fields are applied to the heart to give cardiac output on an emergency basis until the arrhythmia ceases or other intervention takes place. The device is used as a stand alone external or internal device, or as a backup to an ICD, atrial defibrillator, or an anti-tachycardia pacemaker. The method and apparatus maintain some cardiac output and not necessarily defibrillation. Excerpt(s): The invention relates to the field of therapies for cardiac arrhythmias, and more particularly, to a method and an apparatus for forcing cardiac output by delivering a pulsatile electrical field to the heart during fibrillation or a hemodynamically compromising tachycardia. Approximately 400,000 Americans succumb to ventricular fibrillation each year. It is known that ventricular fibrillation, a usually fatal heart arrhythmia, can only be terminated by the application of an electrical shock delivered to the heart. This is through electrodes applied to the chest connected to an external defibrillator or electrodes implanted within the body connected to an implantable cardioverter defibrillator (ICD). Paramedics cannot usually respond rapidly enough with their external defibrillators to restore life. New methods of dealing with this problem include less expensive external defibrillators (and thus more readily available) and smaller implantable defibrillators. Since the first use on humans of a completely implantable cardiac defibrillator in 1980, research has focused on making them continually smaller and more efficient by reducing the defibrillation threshold energy level. The goal has been to reduce the size of the implantable device so that it could be implanted prophylactically, i.e., in high risk patients before an episode of ventricular fibrillation. An ICD includes an electrical pulse generator and an arrhythmia detection circuit coupled to the heart by a series of two or more electrodes implanted in the body. A battery power supply, and one or more charge storage capacitors are used for delivering defibrillation shocks in the form of electrical current pulses to the heart. These devices try to restore normal rhythm from the fibrillation. While it works well at restoring normal function, the ICD is large in size and not practical for a truly prophylactic device. A small device capable of maintaining minimal cardiac output, in high risk patients, prior to admission into an emergency room is needed. Web site: http://www.delphion.com/details?pn=US06314319__

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Method and device for multi-chamber cardiac pacing in response to a tachycardia Inventor(s): Lu; Richard (Thousand Oaks, CA) Assignee(s): Pacesetter, Inc. (sylmar, Ca) Patent Number: 6,654,639 Date filed: May 7, 2001

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Abstract: An apparatus and method for performing multi-chamber anti-tachycardia pacing (ATP) in response to a tachycardia that is of particular use in an implantable cardiac stimulation device. The expected benefits of such a multi-chamber ATP include improved hemodynamic performance and the ability to terminate the tachycardia sooner. Embodiments of the present invention use an intrinsic chamber activation sequence and associated interchamber time delays, preferably automatically detected during a period of time when a pathologic tachycardia is not present, to treat a pathologic tachycardia should it occur. Such a device monitors two or more chambers of the patient's heart, i.e., the controlled chambers, and in the event a tachycardia is detected, the device determines the chamber which originated the tachycardia. The device then calculates anti-tachycardia pacing (ATP) cycle lengths, typically as percentages of the detected tachycardia cycle length of the chamber where the tachycardia originated, and begins pacing the controlled chambers according to the intrinsic chamber activation sequence and interchamber delays (initially synchronized relative to a cardiac signal from the chamber which originated the tachycardia) at the ATP cycle lengths for a predefined period or until the tachycardia ends. Optionally, embodiments of the present invention may additionally include a hemodynamic sensor and may adaptively alter the activation sequence and/or interchamber time delays in response to feedback from the hemodynamic sensor. Excerpt(s): The present invention is generally directed to an implantable medical device, e.g., a cardiac stimulation device, and is particularly directed to a method for treating tachycardia in a multi-chamber cardiac stimulation device. Implantable cardiac stimulation devices are well known in the art. They include implantable pacemakers which provide stimulation pulses to cause a heart, which may beat too slowly or at an irregular rate, to beat at a controlled normal rate. They also include defibrillators, which detect when the atria and/or the ventricles of the heart are in fibrillation or a pathologic tachycardia and apply cardioverting or defibrillating electrical energy to the heart to restore the heart to a normal rhythm. Implantable cardiac stimulation devices may also include the combined functions of a pacemaker and a defibrillator. The treatment and avoidance of ventricular fibrillation, is significant since without needed treatment, death may occur within minutes of an episode's onset. It is estimated that such "sudden cardiac death" may result in 350,000 to 450,000 people per year, approximately one every minute. Tachycardia, i.e., an elevated cardiac rate typically in excess of 100 bpm (beats per minute), while potentially being symptomatic to the patient is generally not fatal. However, a tachycardia episode may accelerate either directly or via progression of the disease process into fibrillation and death may result. Therefore, it is desirable and potentially necessary to treat a tachycardia episode to avoid such a fatal progression. Web site: http://www.delphion.com/details?pn=US06654639__ •

Method and device for sensing atrial depolarizations during ventricular tachycardia Inventor(s): Kim; Jaeho (Redmond, WA) Assignee(s): Cardiac Pacemakers, Inc. (st. Paul, Mn) Patent Number: 6,643,547 Date filed: March 30, 2001 Abstract: A cardiac rhythm management device is disclosed which incorporates an improved method for sensing atrial depolarizations during episodes of ventricular tachycardia. The atrial sensing channel is blanked for a specified blanking interval after

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detection of a ventricular sense. When the ventricular rate is above a specified limit rate, the blanking interval for the atrial sensing channel is either shortened or blanking is discontinued altogether in order to allow sensing of atrial depolarizations that occur shortly after a ventricular sense. Excerpt(s): This invention pertains to cardiac rhythm management devices and methods. In particular, the invention relates to methods for the detection of atrial and ventricular tachyarrhythmias. Tachyarrhythmias are abnormal heart rhythms characterized by a rapid heart rate. Examples of tachyarrhythmias include supraventricular tachycardias such as atrial tachycardia and atrial fibrillation. The most dangerous tachyarrythmias, however, are ventricular tachycardia and ventricular fibrillation. Ventricular rhythms occur when an excitatory focus in the ventricle usurps control of the heart rate from the sinoatrial node. The result is rapid and irregular contraction of the ventricles out of electromechanical synchrony with the atria. Most ventricular rhythms exhibit an abnormal QRS complex in an electrocardiogram because they do not use the normal ventricular conduction system, the depolarization spreading instead from the excitatory focus directly into the myocardium. Ventricular tachycardia is characterized by distorted QRS complexes occurring at a rapid rate, while ventricular fibrillation is diagnosed when the ventricle depolarizes in a chaotic fashion with no recognizable QRS complexes. Both ventricular tachycardia and ventricular fibrillation are hemodynamically compromising, and both can be life-threatening. Ventricular fibrillation, however, causes circulatory arrest within seconds and is the most common cause of sudden cardiac death. Cardioversion (an electrical shock delivered to the heart synchronously with the QRS complex) and defibrillation (an electrical shock delivered without synchronization to the QRS complex to terminate ventricular fibrillation) can be used to terminate most tachycardias. The electric shock terminates the tachycardia by depolarizing all excitable myocardium to render it refractory to further excitation. Implantable cardioverter/defibrillators (ICD's) provide this kind of therapy by delivering a shock pulse to the heart when fibrillation is detected by the device. Web site: http://www.delphion.com/details?pn=US06643547__ •

Methods and apparatus for tachycardia rate hysteresis for dual-chamber cardiac stimulators Inventor(s): Armstrong; Randolph Kerry (Missouri City, TX), Cook; Douglas Jason (Minnetonka, MN) Assignee(s): Intermedics, Inc. (angleton, Tx) Patent Number: 6,510,343 Date filed: March 19, 2001 Abstract: It has been determined that certain dual-chambered cardiac stimulators may operate in a region in which an atrial pacing event may obscure the detection of a ventricular tachyarrhythmia Various exemplary techniques may be used to improve the ability of dual-chamber cardiac stimulators to detect such ventricular events. In accordance with one technique, it is determined whether a ventricular event should be classified as a ventricular tachyarrhythmia. If not, the VA interval is restarted as usual. However, if the ventricular event may be classified as a ventricular tachyarrhythmia, it is determined whether the ventricular event falls within the region in which an atrial pacing event may obscure its detection. If not, then the VA interval is restarted as usual. However, if the ventricular event falls within this region, the VA interval is restarted with the VT rate detection boundary. This has the effect of lengthening the VA interval

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and the AA interval in this region so that atrial pacing events will not obscure the sensing and treatment of ventricular tachyarrhythmias in the region. Excerpt(s): The present invention relates generally to cardiac stimulators and, more particularly, to dual-chamber cardiac stimulators that have an improved ability to detect tachyarrhythmias. As most people are aware, the human heart is an organ having four chambers. A septum divides the heart in half, with each half having two chambers. The upper chambers are referred to as the left and right atria, and the lower chambers are referred to as the left and right ventricles. Deoxygenated blood enters the right atrium through the pulmonary veins. Contraction of the right atrium and of the right ventricle pump the deoxygenated blood through the pulmonary arteries to the lungs where the blood is oxygenated. This oxygenated blood is carried to the left atrium by the pulmonary veins. From this cavity, the oxygenated blood passes to the left ventricle and is pumped to a large artery, the aorta, which delivers the pure blood to the other portions of the body through the various branches of the vascular system. In the normal human heart, the sinus node (generally located near the junction of the superior vena cava and the right atrium) constitutes the primary natural pacemaker by which rhyhnic electrical excitation is developed. The cardiac impulse arising from the sinus node is transmitted to the two atrial chambers. In response to this excitation, the atria contract, pumping blood from those chambers into the respective ventricles. The impulse is transmitted to the ventricles through the atrioventricular (AV) node to cause the ventricles to contract. This action is repeated in a rhythmic cardiac cycle in which the atrial and ventricular chambers alternately contract and pump, then relax and fill. Oneway valves between the atrial and ventricular chambers in the right and left sides of the heart and at the exits of the right and left ventricles prevent backflow of the blood as it moves through the heart and the circulatory system. Web site: http://www.delphion.com/details?pn=US06510343__ •

Multiple stage morphology-based system detecting ventricular tachycardia and supraventricular tachycardia Inventor(s): Hsu; William (Circle Pines, MN), Marcovecchio; Alan F. (Minneapolis, MN) Assignee(s): Cardiac Pacemakers, Inc. (st. Paul, Mn) Patent Number: 6,275,732 Date filed: June 17, 1998 Abstract: A system for detecting ventricular tachycardia and supraventricular tachycardia using a multiple stage morphology based system. Cardiac signals are sensed from a patient's heart and analyzed for the occurrence of a tachycardia event. When a tachycardia event is detected, the method and system analyzes a plurality of features of the sensed cardiac signals in two or more discrimination stages. Each of the two or more discrimination stages classify the tachycardia event as either a ventricular tachycardia or a candidate supraventricular tachycardia event. When a discrimination stage detects the occurrence of a ventricular tachycardia, therapy is delivered to the heart to treat the ventricular tachycardia. Excerpt(s): This invention relates generally to the field of medical devices, and more particularly to a method and system for discriminating and classifying supraventricular tachycardia and ventricular tachycardia events. Recent prospective clinical trials have shown that cardioverter-defibrillators, such as implantable cardioverter-defibrillators (ICDs), reduce sudden arrhythmic death and favorably impact overall mortality in

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patients at risk for spontaneous ventricular tachyarrhythmia. Cardioverter-defibrillator systems are designed to provide therapy when rapid ventricular activation rates are sensed. However, rapid ventricular rhythms can occur in the presence of a supraventricular tachycardia (SVT). When therapy is applied in response to SVT (in absence of a ventricular tachycardia, VT, or ventricular fibrillation, VF), the therapy is classified as clinically "inappropriate", even though the cardioverter-defibrillator responded appropriately to an elevated ventricular rate. Cardioverter-defibrillators may deliver inappropriate ventricular therapy to patients afflicted with non-malignant SVTs. These inappropriate therapies may be delivered due to the device's inability to reliably discriminate SVT from malignant VT. Web site: http://www.delphion.com/details?pn=US06275732__ •

Pacemaker system for preventing ventricular tachycardia Inventor(s): De Vries; Bernhard A. P. (Dieren, NL), Stoop; Gustaaf A. P. (Dieren, NL), Van Groeningen; Christianus J. J. E. (Utrecht, NL), Van Oort; Geeske (Nieuwleusen, NL) Assignee(s): Medtronic, Inc. (minneapolis, Mn) Patent Number: 6,370,431 Date filed: January 27, 1999 Abstract: There is provided a pacemaker system which includes intervention for overdriving the patient's natural heart rate in the event of a sensed incipient ventricular arrhythmia condition, and particularly torsades de pointes. The pacemaker continually acquires QT signals and analyzes them for respective properties, updating statistical information relating to the properties. In a preferred embodiment, the pacemaker analyzes QT interval, QT dispersion, time derivative of the QT interval, and/or T-wave amplitude and determines an intervention for pacing therapy based upon changes to these properties. The pacemaker also monitors premature ventricular beats and generates data representative of such occurrences, which data is used alone or in combination with QT data in determining whether intervention is indicated, for adjusting the intervention pacing rate. There is thus provided a systematic approach for monitoring relevant data so as to reliably determine when intervention pacing therapy is needed, and for adjusting the intervention pacing rate. Excerpt(s): This invention relates to cardiac pacing systems and, more particularly, pacing systems having a capability of detecting and treating long QT syndrome. It is known that prolongation of the QT interval frequently results in serious ventricular arrhythmias, and might be a predictor of torsades de pointes (TdP) and sudden death. See, "Electrophysiology of Torsades de Pointes," Fontaine et al., World Symposium on Cardiac Pacing, 6.sup.th, Montreal, PACESYMP, 1979, p. 6.3. As set forth in the Fontain et al. article, TdP is manifested by an ECG pattern which occurs as a transient lifethreatening ventricular arrhythmia, frequently announced by bradycardia, long QT intervals, very large T waves and premature ventricular contractions (PVCs). The term Ventricular Extra Systole (VES) is used herein synonymously with PVC. The premature ventricular beats that occur at the onset of long QT syndrome appear around the end of the large T waves, and the number of such VESs increases with time, leading to couplets or triplets and eventually to a degeneration of the rapid arrhythmia which characterizes TdP. A VES originates in the ventricle, and is considered a PVC when it comes "early" with respect to the previous VS. More broadly, there is a need in the art for providing a more systematic and reliable means of determining when patient conditions suggest the onset of a dangerous ventricular arrhythmia, and for providing an effective overdrive

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pacing therapy to prevent such arrhythmia. For instance, it is known that patients can be vulnerable to ventricular tachycardia (VT) during the awakening hours, while TdP emerging from Long QT syndrome and other ventricular arrhythmias can occur at any time. Thus, there is a need for a more reliable pacemaker technique for detecting the onset of a ventricular arrhythmia whenever it might occur, and for providing appropriate pacing therapy. Web site: http://www.delphion.com/details?pn=US06370431__ •

QRST subtraction using an adaptive template for analysis of TU wave obscured atrial activity Inventor(s): Groenewegen; Arne Sippens (Burlingame, CA), Lesh; Michael D. (Mill Valley, CA), Mlynash; Michael D. (Mountain View, CA) Assignee(s): The Regents of the University of California (oakland, Ca) Patent Number: 6,615,075 Date filed: March 14, 2001 Abstract: The present invention provides a noninvasive localization, characterization and classification apparatus and method for cardiac arrhythmias. The invention enables discrete isolation of the intricate spatial and temporal detail in morphology of the atrial activity of interest from superimposed ventricular activity of a preceding heartbeat in a particular arrhythmia. An adaptive QRST subtraction template is used that is modulated for discrepancies in voltage and rate between the QRST template and arrhythmia signal. The QRST template modulation is accomplished by using one or more fiducial points and windows that are annotated in both the QRST template and the arrhythmia signal. The invention includes, but is not limited to, the isolation of atrial activity that are commonly known as: (1) P waves in case of focal atrial fibrillation, atrial tachycardia, and orthodromic AV reentrant tachycardia; (2) fibrillation waves in case of chronic atrial fibrillation; and (3) flutter waves in case of atrial flutter. Excerpt(s): This invention relates generally to electrocardiographic localization and classification of cardiac arrhythmias. More particularly, the present invention relates to noninvasive analysis of TU wave obscured atrial activity. An arrhythmia is any deviation from or disturbance of the normal heart rhythm. This is when the heart's natural pacemaker develops an abnormal rate or rhythm (e.g. a tachycardia where the heart rate is faster than normal), the normal conduction pathway is interrupted, an abnormal or accessory conduction pathway controls the rhythm, or when another part of the heart takes over as an ectopic pacemaker. Arrhythmias may be benign, life threatening or even fatal depending on the type of arrhythmia. Several different types of arrhythmias can be distinguished, for example atrial tachycardia, atrioventricular (AV) node reentrant tachycardia, atrial fibrillation, atrial flutter, and ventricular tachycardia. Although electrocardiographic arrhythmia evaluation is currently feasible by capturing spontaneous tachycardia episodes via ambulatory or emergency electrocardiogram (ECG) recording, analysis of the timing and presumed origin of atrial activation on the body surface is frequently hampered by the simultaneous occurrence of the higher voltage ventricular activation or recovery potentials. During both focal and incisional reentrant atrial tachycardia, the low-amplitude P wave (atrial activity) may be obscured by the preceding high-amplitude QRST segment (ventricular activity). Difficulties are encountered when visually assessing the P wave morphology of TU wave superimposed ectopic atrial beats that are critically related to atrial fibrillation triggered by a focal source, typically situated in one of the pulmonary veins. Similarly,

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localization of the atrial insertion site using the retrograde P wave morphology obtained during orthodromic AV reentrant tachycardia may be difficult due to partial or complete concealment by the TU wave. Web site: http://www.delphion.com/details?pn=US06615075__ •

Safety backup in arrhythmia discrimination algorithm Inventor(s): Clem; Elisabeth (Redwood City, CA), Fain; Eric S. (Menlo Park, CA), Malden; Lisa (Sunny Isles, FL) Assignee(s): Pacesetter, Inc. (sunnyvale, Ca) Patent Number: 6,636,764 Date filed: November 16, 2001 Abstract: In an arrhythmia discrimination algorithm a timer is used to trigger the delivery of therapy when no diagnosis is made within a defined time during a tachycardia episode. Where one or more rhythm discriminators or qualifiers such as morphology, sudden onset, interval stability and AV association is enabled, the timer starts as soon as a ventricular interval or interval average is faster than a programmed maximum time to diagnosis (MTD) cutoff. If the timer times out before the algorithm diagnoses a particular rhythm, a programmed therapy is delivered. In the preferred embodiment, the therapy that is triggered is a function of the most recent detected ventricular rate and the programmed MTD therapy. Excerpt(s): The present invention relates generally to implantable pulse generators for treating cardiac arrhythmias, and more specifically to a safety timeout for use with a method for discrimination between supraventricular and ventricular tachyarrhythmias. One of the most frequent causes of follow-ups for patients with an implantable cardioverter-defibrillator (ICD) is inappropriate therapy. Between 15% and 30% of ICD patients receive inappropriate therapies because of supra-ventricular tachycardias (SVT). Single chamber defibrillators have algorithms such as morphology discrimination, sudden onset and interval stability that can be used to differentiate between ventricular tachycardias (VT) versus those that originate supra-ventricularly, i.e., in the atria. These algorithms have provided increased specificity for SVTs while still maintaining a high level of sensitivity to VT, but inappropriate therapies can still occur. With the advent of dual-chamber defibrillators that sense both in the atrium and ventricle, atrial rate has been used to aid in the identification of VTs and SVTs. This has further increased the specificity for SVTs, but relying solely on the relationships between the rates of atrial and ventricular sensed events can result in erroneous classifications. Existing dual-chamber ICDs have exhibited difficulty in diagnosing certain rhythms correctly such as sinus tachycardia (tach), SVTs with 1:1 ventricular conduction, and VT with 1:1 retrograde conduction. VT with 1:1 retrograde conduction may look like sinus tach if the retrograde conduction interval is quite long. Conversely, sinus tach with first degree AV block can be classified by some schemes as a retrograde VT. Ventricular tachycardia during an atrial tachycardia has also been erroneously detected as SVT. Various diagnostic qualifiers can be implemented for improved discrimination of SVT from VT where the atrial and ventricular rates are the same or when the atrial rate is greater than the ventricular rate. However, they present the possible problem of extending the time required before a diagnosis is made and therapy is delivered. This is particularly problematic where a ventricular tachycardia is hemodynamically compromising or may degrade to ventricular fibrillation. It is desirable to provide a

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safety backup in the discrimination algorithm to ensure therapy is delivered where appropriate. Web site: http://www.delphion.com/details?pn=US06636764__ •

Substituted dicinnamoylquinides and their use in augmentation of adenonsine function Inventor(s): de Paulis; Tomas (Hermitage, TN), Lovinger; David M. (Rockville, MD), Martin; Peter (Nashville, TN) Assignee(s): Vanderbilt University (nashville, Tn) Patent Number: 6,693,128 Date filed: May 10, 2002 Abstract: This invention describes the novel use of alkyl, alkoxyl, halogenyl, or hydroxy substituted dicinnamoylquinides as therapeutic agents for enhancing adenosine levels in the brain and peripheral organs. These agents are particularly useful in treating human diseases or conditions that benefit from acute or chronic elevated levels of adenosine, such as reperfusion injury, coronary or cerebral ischemia, coronary vasoconstriction, paroxysmal supraventricular tachycardia, hypertension, wound healing, diabetes, inflammation, or sleep disturbances. They can also be used to protect normal cells from chemotoxicity in patients undergoing cancer therapy, and reverse the behavioral effects of caffeine intake. Excerpt(s): The present invention relates generally to the field of use of alkyl, alkoxyl, halogenyl, or hydroxyl substituted dicinnamoylquinides. Specifically, the present invention relates to the use of the above-mentioned compounds to treat diseases or conditions that improve from either an acute or chronic increase in adenosine levels. Adenosine is a neuromodulator known to produce profound effects on blood flow, neurotransmission, cellular functions, and metabolism. Intracellular levels of adenosine are disclosed to be maintained by an active transport of adenosine across the cell membrane by means of a carrier-mediated, saturable nucleoside transporter, consisting of a 50 kDa protein in the form of a dimer (Thorn and Jarvis, Gen Pharmacol 27, 613-620 (1996)). This transporter protein is widely distributed in thalamic, cortical, and particularly in striatal neurons in the human brain (Glass et al, Brain Res 710, 79-91 (1996), Jennings et al, Neuropharmacol 40, 722-731 (2001)), where it regulates adenosinedopamine interactions (Dunwiddie and Masino, Ann Rev Neurosci 24, 31-55 (2001)). Of all mammals studied, the human transporter is disclosed to be one of the most sensitive to adenosine (Hammond, N-S Arch Pharmacol 361, 373-382 (2000)), resulting in an extremely short half-life of adenosine in blood. Inhibition of the adenosine transporter is disclosed to prevent the intracellular metabolism of adenosine and prolongs the presence of high levels of adenosine (Thorn and Jarvis, Gen Pharmacol 27, 613-620 (1996). This increased level of adenosine in brain causes stimulation of adenosine receptor subtypes, similar to the effects seen from unselective adenosine receptor agonizes. Activation of the adenosine A.sub.2B receptor was found to increase vascular endothelial growth factor production, resulting in angiogenic neovascularization (Grant et al, Circ Res 85, 699-706 (1999). Recent studies have demonstrated that agonists for the adenosine A.sub.3 receptor have antiinflammatory properties (Fishman et al, J. Cell Physiol 183, 393-398 (2000)). Both agonists at the adenosine A.sub.1 and A.sub.3 receptors have shown cardioprotective activity in man (Baraldi et al, Ed Res Rev 20, 103128 (2000)), and conjugate compounds of potent adenosine A.sub.1 and A.sub.3 receptor agonists have shown full cardioprotection in a myocyte model of ischemia (Jacobson et

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al, J. Biol Chem 275, 30272-30279 (2000)). Based on the discovery that certain naturally occurring 4-hydroxycinnamoyl di-esters of quinic acid gamma-lactone in roasted coffee (Hucke et al, Z. Lebensm Unters Forsch 180, 479-484 (1985)), but not in tea or any other caffeine containing beverages, inhibits the human adenosine transporter (de Pails et al, Eur J Pharmacol 442, 213-221 (2002)), the present invention provides, in part, methods of using 3,4-disubstituted cinnamoyl esters of quinic acid 1,5-lactone, exemplified by Formula 1, having no substituent, or a halogen atom or a hydroxyl, alkyl or alkoxyl group in either of the aromatic 3-, 4- and 5-positions to inhibit the human adenosine transporter. By inhibiting the adenosine transporter, the metabolism of intracellular adenosine is prevented resulting in increased levels of extracellular adenosine. Web site: http://www.delphion.com/details?pn=US06693128__ •

System and method for complexity analysis-based cardiac tachyarrhythmia detection Inventor(s): Lin; Dongping (Irvine, CA), Zhang; Xu-Sheng (Santa Ana Heights, CA) Assignee(s): Cardiac Science Inc. (irvine, Ca) Patent Number: 6,490,478 Date filed: September 25, 2000 Abstract: A system and method based on electrocardiogram (ECG) complexity analysis for real-time detecting shockable ventricular fibrillation (VF) and ventricular tachycardia (VT), and discriminating them from non-shockable tachyarrhythmia (e.g. supraventricular tachycardia (SVT) and atrial fibrillation (AF)) and high-frequency noise. In the disclosed invention, complexity measure CM (0 to 100), quantitatively characterizing the complexity nature of the non-linear dynamics underlying cardiac arrhythmia, is extracted from the sensed patient ECG signal using ECG complexity analysis. From the calculated complexity measure, by three thresholds (low complexity threshold (LCT), mediate complexity threshold (MCT), and high complexity threshold (HCT)), different kinds of tachyarrhythmia (i.e. heart rate (HR) above a preset rate threshold) and high-frequency noise are discriminated from each other: for nonshockable tachyarrhythmia, CM.ltoreq.LCT; for VT, LCT
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shockable VT and VF and while avoiding unnecessary shocks possibly caused by nonshockable tachyarrhythmias (e.g. supraventricular tachycardia (SVT), atrial fibrillation (AF), etc.) and some high-frequency noise commonly encountered under practical situations. Since electrical shocks always have adverse affects on the myocardium, another primary goal of all cardiac therapies is to minimize the number and energy level of electrical signals delivered to the patient. To this end, VT, which requires much lower energy levels for effective therapy, must be effectively differentiated from VF. Moreover, the safety of a device, as well as its ease of use, extent of automatic operation, and widespread acceptance also depend on the performance of the arrhythmia detection system and method. Web site: http://www.delphion.com/details?pn=US06490478__

Patent Applications on Tachycardia As of December 2000, U.S. patent applications are open to public viewing.9 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to tachycardia: •

Algorithm for discrimination of 1:1 tachycardias Inventor(s): Lovett, Eric G.; (Roseville, MN), Thompson, Julie Ann; (White Bear Lake, MN) Correspondence: Schwegman, Lundberg, Woessner & Kluth, P.A.; P.O. Box 2938; Minneapolis; MN; 55402; US Patent Application Number: 20030074026 Date filed: October 17, 2001 Abstract: An algorithm for detection of tachycardias and for discriminating between supraventricular tachycardia (SVT) and ventricular tachycardia (VT) when a 1:1 tachycardia condition is present that can be implemented in an implantable cardiac rhythm management device. Variability measures of AV and VA intervals during the tachycardia are computed and used to distinguish between SVT and VT. Excerpt(s): This invention pertains to methods and systems for treating cardiac arrhythmias. In particular, it deals with discriminating between different types of tachyarrhythmias. Tachyarrhythmias are abnormal heart rhythms characterized by a rapid rate, typically expressed in units of beats per minute (bpm), that can originate in either the ventricles or the atria. Examples of tachyarrhythmias include sinus tachycardia, atrial tachycardia, atrial fibrillation, ventricular tachycardia, and ventricular fibrillation. The most dangerous tachyarrythmias are those that have their origin in the ventricles, namely ventricular tachycardia (VT) and ventricular fibrillation (VF). Ventricular rhythms occur when re-entry of a depolarizing wavefront in areas of the ventricular myocardium with different conduction characteristics becomes selfsustaining or when an excitatory focus in the ventricle usurps control of the heart rate from the normal physiological pacemaker of the heart, the sino-atrial node. The result is rapid contraction of the ventricles out of electromechanical synchrony with the atria. Most ventricular rhythms exhibit an abnormal QRS complex in an electrocardiogram

9

This has been a common practice outside the United States prior to December 2000.

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(ECG) because they do not use the specialized conduction system of the ventricles, the depolarization spreading instead from the excitatory focus or point of re-entry directly into the myocardium. In ventricular tachycardia, the ventricles contract rapidly and produce distorted QRS complexes in an ECG. Ventricular fibrillation, on the other hand, occurs when the ventricles depolarize at an even more rapid rate and in a chaotic fashion, resulting in QRS complexes of constantly changing shape and virtually no effective pumping action. Both ventricular tachycardia and ventricular fibrillation are hemodynamically compromising, and both can be life-threatening. Ventricular fibrillation, however, causes circulatory arrest within seconds and is the most common cause of sudden cardiac death. Cardiac rhythm management devices known as implantable cardioverter/defibrillators (ICDs) are designed to treat ventricular tachyarrhythmias by delivering an electrical shock pulse to the heart. Cardioversion and/or defibrillation can be used to terminate most tachyarrhythmias, including VT and VF. The electric shock terminates the tachyarrhythmia by depolarizing all of the myocardium simultaneously and rendering it refractory. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Anti-tachycardia pacing based on multi-site electrograms Inventor(s): Struble, Chester L.; (Eljsden, NL) Correspondence: Medtronic, INC.; 710 Medtronic Parkway NE; Ms-lc340; Minneapolis; MN; 55432-5604; US Patent Application Number: 20030199932 Date filed: April 22, 2002 Abstract: In one embodiment, a method includes sensing depolarizations of a heart at a plurality of different locations, and determining a sequence of the sensed depolarizations. The method may further include identifying a tachycardia condition and stimulating the heart at the plurality of locations based on the determined sequence. For example, the method may be implemented by an implantable medical device in order to improve anti-tachycardia pacing (ATP). Excerpt(s): The invention relates to cardiac pacing systems and, more particularly, to multiple-lead cardiac pacing systems. An arrhythmia is a disturbance in the normal rate, rhythm or conduction of the heartbeat. Arrhythmia may originate in an atrium or a ventricle. Atrial tachycardia (AT) and ventricular tachycardia (VT) (collectively referred to as tachycardia), are forms of arrhythmia in which the atria or ventricles contract at a high rate, e.g., 100 or more beats per minute. Atrial fibrillation (AF) and ventricular fibrillation (VF) (collectively referred to as fibrillation) are other forms of arrhythmia, characterized by a chaotic and turbulent activation of atrial or ventricle wall tissue. The number of depolarizations per minute during fibrillation can exceed 400. In addition, the fibrillation stimuli can occur in the refractory period of the surrounding myocardium. Tachycardia can lead to fibrillation, which in turn can be life threatening. Tachycardia is also associated with other low cardiac output symptoms, such as fatigue. Many tachycardias are episodic, marked by abrupt onset but also abrupt termination. Still, tachycardia can cause considerable patient distress. Moreover, if untreated, tachycardia can lead to other dangerous life-threatening conditions, such as the development of blood clots which can cause stroke and possibly death. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Apparatus and method for cardiac ablation Inventor(s): Desai, Jawahar M.; (Roseville, CA) Correspondence: Parsons Hsue & DE Runtz Llp; 655 Montgomery Street; Suite 1800; San Francisco; CA; 94111; US Patent Application Number: 20030181819 Date filed: February 11, 2003 Abstract: A system and method for cardiac mapping and ablation include a multielectrode catheter introduced percutaneously into a subject's heart and deployable adjacent to various endocardial sites. The electrodes are connectable to a mapping unit, an ablation power unit a pacing unit, all of which are under computer control. Intracardiac electrogram signals emanated from a tachycardia site of origin are detectable by the electrodes. Their arrival times are processed to generate various visual maps to provide real-time guidance for steering the catheter to the tachycardia site of origin. In another aspect, the system also include a physical imaging system which is capable of providing different imaged physical views of the catheter and the heart. These physical views are incorporated into the various visual maps to provide a more physical representation. Once the electrodes are on top of the tachycardia site of origin, electrical energy is supplied by the ablation power unit to effect ablation. Excerpt(s): This is a continuation-in-part of application Ser. No. 08/029,771, filed Mar. 11, 1993. This invention relates to medical devices and, in particular, a system and technique of employing multi-electrode catheters for cardiac mapping and ablation. Cardiac dysrhythmias are commonly known as irregular heart beats or racing heart. Two such heart rhythm irregularities are the Wolff-Parkinson-white syndrome and atrioventricular (AV) nodal reentrant tachycardia. These conditions are caused by an extraneous strand of conducting fibers in the heart that provides an abnormal shortcircuit pathway for electric impulses normally conducting in the heart. For example, in one type of Wolff-Parkinson-White syndrome the accessory pathway causes the electric impulses that normally travel from the upper to the lower chamber of the heart to be fed back to the upper chamber. Another common type of cardiac dysrhythmias is ventricular tachycardia (VT), which is a complication of a heart attack or reduction of blood supply to an area of heart muscle, and is a life threatening arrhythmia. All these types of dysrhythmias can usually be traced to one or more pathological "sites of origin" or tachycardia foci in the heart. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Apparatus and method for multi-site anti-tachycardia pacing Inventor(s): Kramer, Andrew P.; (Stillwater, MN), Spinelli, Julio C.; (Shoreview, MN), Stahmann, Jeffrey E.; (Ramsey, MN), Zhu, Qingsheng; (Little Canada, MN) Correspondence: Schwegman, Lundberg, Woessner & Kluth, P.A.; P.O. Box 2938; Minneapolis; MN; 55402; US Patent Application Number: 20030120315 Date filed: December 20, 2001 Abstract: An apparatus and method for treating ventricular tachycardia in which paces are delivered to the ventricles at multiple pacing sites in accordance with an antitachycardia pacing protocol. Paces are delivered at a selected offset interval in a manner

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that both resynchronizes ventricular contractions and increases the probability of terminating the tachycardia. Excerpt(s): This invention pertains to systems and methods for treating arrhythmias with electrical stimulation. Also included within the concept of cardiac rhythm is the manner and degree to which the heart chambers contract during a cardiac cycle to result in the efficient pumping of blood. For example, the heart pumps more effectively when the chambers contract in a coordinated manner. The heart has specialized conduction pathways in both the atria and the ventricles that enable the rapid conduction of excitation (i.e., depolarization) throughout the myocardium. These pathways conduct excitatory impulses from the sino-atrial node to the atrial myocardium, to the atrioventricular node, and thence to the ventricular myocardium to result in a coordinated contraction of both atria and both ventricles. This both synchronizes the contractions of the muscle fibers of each chamber and synchronizes the contraction of each atrium or ventricle with the contralateral atrium or ventricle. Without the synchronization afforded by the normally functioning specialized conduction pathways, the heart's pumping efficiency is greatly diminished. Patients who exhibit pathology of these conduction pathways, such as bundle branch blocks, can thus suffer compromised cardiac output. Heart failure refers to a clinical syndrome in which an abnormality of cardiac function causes a below normal cardiac output that can fall below a level adequate to meet the metabolic demand of peripheral tissues. It usually presents as congestive heart failure (CHF) due to the accompanying venous and pulmonary congestion. Heart failure can be due to a variety of etiologies with ischemic heart disease being the most common. Some heart failure patients suffer from some degree of AV block or are chronotropically deficient such that their cardiac output can be improved with conventional bradycardia pacing. Such pacing, however, may result in some degree of uncoordination in atrial and/or ventricular contractions because pacing excitation from a single pacing site is spread throughout the myocardium only via the much slower conducting muscle fibers of either the atria or the ventricles, and not the specialized conduction pathways. Most pacemaker patients can still maintain more than adequate cardiac output with artificial pacing, but the diminishment in cardiac output may be significant in a heart failure patient whose cardiac output is already compromised. Intraventricular and/or interventricular conduction defects are also commonly found in heart failure patients and can contribute to cardiac dysfunction by causing unsynchronized contractions during intrinsic beats. In order to treat these problems, cardiac rhythm management devices have been developed which provide electrical pacing stimulation to one or more heart chambers in an attempt to improve the coordination of atrial and/or ventricular contractions, termed cardiac resynchronization therapy. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Apparatus and method for pacing mode switching during atrial tachyarrhythmias Inventor(s): Kramer, Andrew P.; (Stillwater, MN), Stahmann, Jeffrey E.; (Ramsey, MN) Correspondence: Schwegman,lundberg, Woessner & Kluth, P.A.; P.O. Box 2938; Minneapolis; MN; 55402; US Patent Application Number: 20020082660 Date filed: December 26, 2000 Abstract: A method for operating a cardiac pacemaker in which the mode of operation of the pacemaker is altered in response to detecting an episode of atrial tachycardia. In

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accordance with the invention, the pacemaker's pacing mode is altered in a manner that attempts to maintain hemodynamic stability during the atrial tachycardia. Such a mode switch is particularly applicable to pacemaker patients suffering from some degree of congestive heart failure. Excerpt(s): This application is related to the following co-pending, commonly assigned patent application: "System providing Ventricular Pacing and Biventricular Coordination," Ser. No. 09/316,588 (Attorney Docket No. 00279.160US1), which disclosure is herein incorporated by reference in its entirety. This invention pertains to cardiac pacemakers and methods for operating such devices. In particular, the invention relates to methods for cardiac pacing during an atrial tachyarrhythmia. Congestive heart failure (CHF) is a clinical syndrome in which an abnormality of cardiac function causes cardiac output to fall below a level adequate to meet the metabolic demand of peripheral tissues. CHF can be due to a variety of etiologies with that due to ischemic heart disease being the most common. Some form of cardiac pacing can often benefit CHF patients. For example, sinus node dysfunction resulting in bradycardia can contribute to heart failure which can be corrected with conventional bradycardia pacing. Also, some CHF patients suffer from some degree of AV block such that their cardiac output is improved by synchronizing atrial and ventricular contractions with dualchamber pacing using a programmed AV delay time (i.e., atrial triggered ventricular pacing or AV sequential pacing). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Apparatus and method for treating ventricular tachyarrhythmias Inventor(s): Dreher, Robert D.; (Roseville, MN), Gilkerson, James O.; (Stillwater, MN), Krig, David B.; (Brooklyn Park, MN), Linder, William J.; (Golden Valley, MN), Wald, Jan D.; (Edina, MN), Zimmer, William L.; (Roseville, MN) Correspondence: Schwegman, Lundberg, Woessner & Kluth, P.A.; P.O. Box 2938; Minneapolis; MN; 55402; US Patent Application Number: 20020107552 Date filed: November 13, 2001 Abstract: A system and method for selectively treating a ventricular tachycardia based on sensed atrial and ventricular intervals from the patient's heart. A detection window of the ten most recent atrial and ventricular intervals are analyzed for the occurrence of either tachycardia or fibrillation. When a majority of the sensed intervals are satisfied, the apparatus starts a duration time interval. Ventricular intervals and atrial intervals are compare, ventricular interval greater than the atrial interval by a bias factor the system delivers tachycardia therapy to the heart. Alternatively, the method withholds tachycardia therapy to the heart when the atrial rate is classified as atrial fibrillation and the ventricular response is unstable. Excerpt(s): This application claims the benefit under 35 USC.sctn.119(e) of U.S. Provisional Application No. 60/045212, filed Apr. 30, 1997. The present invention relates generally to implantable pulse generators and in particular to implantable cardioverterdefibrillators for treating ventricular tachyarrhythmias. Implantable cardioverterdefibrillators (ICDs) have evolved significantly since their clinical introduction by Miroski in 1980. Initial ICDs were designed to recognize ventricular fibrillation and to deliver high-energy shocks in an attempt to treat the arrhythmia However, clinical electrophysiology research indicated that an ICD capable of recognizing and treating

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ventricular tachycardias as well as ventricular fibrillation was useful for prevention of arrhythmic death. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Arrhythmia notification Inventor(s): Hess, Michael F.; (Minneapolis, MN), Mehra, Rahul; (Stillwater, MN), Sheth, Nirav Vijay; (Coon Rapids, MN), Ujhelyi, Michael R.; (Maple Grove, MN) Correspondence: Medtronic, INC.; 710 Medtronic Parkway NE; Ms-lc340; Minneapolis; MN; 55432-5604; US Patent Application Number: 20030050566 Date filed: September 7, 2001 Abstract: Notifying a patient or another person of an arrhythmia episode facilitates management of atrial fibrillation (AF) and other arrhythmias, including atrial flutter, atrial tachycardia, and supra ventricular tachycardia, thus enabling the patient to take corrective action even in the absence of symptoms or latent cardiac problems. For example, the patient may be prompted to take a medication, to initiate electrical therapy in the form of pacing or defibrillation, or to seek medical attention. Notification may be issued either by an implantable medical device or by an external device in communication with the implantable medical device. Various types of notifications may be issued under a variety of conditions, some of which may be associated with the duration of an episode. Excerpt(s): The invention relates to implantable medical devices. More particularly, the invention relates to implantable medical devices for treatment of cardiac arrhythmias. The heart functions by generating electrical signals to initiate physical contractions of various portions of the heart in a specific and timed sequence. These electrical signals are generated by the sinus node in the upper right atrial wall near the base of the heart and are conducted through the upper heart chambers, i.e., the right and left atria, and cause them to contract in a synchronous manner. The contractions force the blood contained in the atria into the right and left ventricles, or lower heart chambers. An electrical depolarization wave then travels through and around the ventricles, causing the ventricles to contract and force the blood throughout the vascular system. The contraction of the right and left ventricles proceeds in an organized fashion that optimizes emptying of the ventricles. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Atrial tachycardia termination sensing Inventor(s): Hettrick, Douglas A.; (Blaine, MN), Mittelstadt, Jacqueline; (Milwaukee, WI) Correspondence: Medtronic, INC.; 710 Medtronic Parkway NE; Ms-lc340; Minneapolis; MN; 55432-5604; US Patent Application Number: 20040064160 Date filed: September 30, 2002 Abstract: Techniques for preventing inadvertent detection of AT termination may involve predicting potential undersensing of atrial events, and delaying detection of AT termination when undersensing of atrial events is predicted. For example, an

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implantable medical device may measure ventricular-atrial (VA) intervals of a heart rhythm using tracked atrial and ventricular events. The device calculates a slope of the series of the VA intervals, and estimates a prospective VA interval using the calculated slope and the most recently measured VA interval. The device determines whether the estimated VA interval is within a threshold range. When the estimated VA interval is outside of the threshold range, the device predicts possible undersensing of atrial events and delays detection of the AT episode termination. The delay detection of AT episode termination improves the accuracy of information collected by event counters. Excerpt(s): The invention relates to cardiac pacing systems and, more particularly, to systems for delivering atrial pacing therapies to treat atrial tachycardia. An arrhythmia is a disturbance in the normal rate, rhythm or conduction of the heartbeat. An atrial arrhythmia originates in the atria. Atrial tachycardia (AT), one form of atrial arrhythmia, is a condition in which the atria contract at a high rate, e.g., 100 or more beats per minute. Atrial fibrillation (AF), another form of atrial arrhythmia, is characterized by a chaotic and turbulent activation of atrial wall tissue. AT can lead to AF, which in turn can be life threatening. In general, the invention is directed to techniques for preventing inadvertent detection of AT termination. The techniques may involve predicting potential undersensing of atrial events, and delaying detection of AT termination when undersensing is predicted. Undersensing of atrial events may occur, for example, during the blanking interval following delivery of a ventricular pacing pulse. Due to undersensing, a continuing AT rhythm can be interpreted as a regular rhythm, resulting in detection of an AT termination. The predictive techniques described herein can be used to recognize undersensing, and thereby prevent inadvertent detection of AT termination. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Automated reapplication of atrial pacing therapies Inventor(s): Brown, Mark L.; (North Oaks, MN), Hess, Michael F.; (Minneapolis, MN), Mehra, Rahul; (Stillwater, MN), Ritscher, David E.; (Golden Vallet, MN), Sheth, Nirav V.; (Coon Rapids, MN), Warman, Eduardo N.; (Maple Grove, MN) Correspondence: Medtronic, INC.; 710 Medtronic Parkway NE; Ms-lc340; Minneapolis; MN; 55432-5604; US Patent Application Number: 20030120317 Date filed: December 20, 2001 Abstract: The invention relates to the use of atrial pacing therapies to treat atrial tachycardia (AT). When an AT episode is detected, an implantable medical device applies an ATP therapy. If the AT episode persists, the ATP therapy may be automatically reapplied at a later time during the course of the same AT episode. In particular, previously used ATP therapies are reapplied when episodic conditions, such as cycle length or cycle regularity, change. Although a particular ATP therapy initially may be unsuccessful in terminating the AT, it may prove successful when the cycle length or regularity of the atrial rhythm changes. As the rhythm slows down, the AT may be more responsive to ATP therapies that were previously unsuccessful. As a result, potentially efficacious ATP therapies can be reapplied to terminate AT episodes, and reduce the number of episodes that require more aggressive termination by painful, atrial shocks.

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Excerpt(s): The invention relates to cardiac pacing systems and, more particularly, to systems for delivering atrial pacing therapies to treat atrial tachycardia. An arrhythmia is a disturbance in the normal rate, rhythm or conduction of the heartbeat. An atrial arrhythmia originates in the atria. Atrial tachycardia (AT), one form of atrial arrhythmia, is a condition in which the atria contract at a high rate, e.g., 100 or more beats per minute. Atrial fibrillation (AF), another form of atrial arrhythmia, is characterized by a chaotic and turbulent activation of atrial wall tissue. The number of depolarizations per minute during AF can exceed 400. In addition, the AF stimuli can occur in the refractory period of the surrounding atrial myocardium. AT can lead to AF, which in turn can be life threatening. Tachycardia is also associated with other low cardiac output symptoms, such as fatigue. Many atrial tachycardias are episodic, marked by abrupt onset but also abrupt termination, but cause considerable patient distress. If untreated, AT can lead to other dangerous life-threatening conditions, such as the development of blood clots which can cause stroke and possibly death. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Cardio therapeutic heart sack Inventor(s): Okuzumi, Yuzi; (Parker, CO) Correspondence: Attention: Melissa Jean Pytel; Merchant & Gould P.C.; P.O. Box 2903; Minneapolis; MN; 55402-0903; US Patent Application Number: 20020151950 Date filed: June 13, 2001 Abstract: This invention relates to implantable heart sack that can be equipped with pacemaker leads and/or defibrillation leads for the treatment of cardiomyopathy, hypertrophic cardiomyopathy, tachycardia, bradycardia, ventricular fibrillation, atrial fibrillation etc. The hear sack was prepared from biocompatible, biostable, implantable polyetherurethane, polycarbonateurethane, silicone, polysiloxaneurethane, polyfluoroethylene, or hydrogenated poly(styrene-butadiene) copolymer. The heart sack is equipped with attached sutures to make it easier to attach onto the heart. The heart sack can be made semipermeable or perforated to have numerous holes. The heart sack can be reinforce with fiber or filament. Ordinary pacemaker leads can be attached to the inner side of the heart sack. However, the pacemaker leads of this invention were prepared from noble metal (gold, platinum, rhodium and platinum-Rhodium alloys) or stainless steel coated, deposited or plated mono-filaments, yarns, braids, cords, wires or films, or cylindrical tubes of polyamide, polyimide, polyester, and/or polypropylene that are encased in multi-lumen insulating tube or coaxial tube made of biocompatible, biostable, implantable polyetherurethane, polycarbonateurethane, silicone, polysiloxaneurethane, polyfluoroethylene, or hydrogenated poly(styrene-butadiene) copolymer. The leads can be mounted onto the inner surface of the heart sack and contoured to the heart. The heart sack can be coated with hydrophilic coating containing an antimicrobial agent that gives the heart sack a low coefficient of friction, excellent biocompatibility and antimicrobial properties. Excerpt(s): This invention relates to a biocompatible, biostable and implantable heart sack which is prepared from biocompatible, biostable and implantable elastomers selected from the group consisting of polyetherurethane, polycarbonateurethane, silicone, poly(siloxane) urethane and/or hydrogenated poly(styrene-butadiene) copolymer for the treatment of cardiomyopathy, hypertrophic cardiomyopathy, tachycardia, bradycardia, ventricular fibrillation, atrial fibrillation etc. The heart sack of

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this invention can be reinforced with mono-filaments, yarns, braids, cords, knitted or woven or non-woven cloth made of a biocompatible, biostable, implantable polyamide, polyimide, polyester, polypropylene, and/or polyurethane etc. The heart sack of this invention can be equipped with pacemaker leads and defibrillation leads. The leads and electrodes of this invention are made of noble metal or stainless steel deposited, coated or plated mono-filaments, yarns, braids, cords, wires, films, cloth and/or cylindrical tubes. The noble metal used for this invention is selected from the group consisting of gold, platinum, rhodium and their alloys. The mono-filaments, yarns, braids, cords, wires, films, cloth or cylindrical tubes materials to be coated, deposited or plated with noble metal are selected from the group consisting of poly(ethylene terephthalate), poly(butylene terephthalate), polyamide, polyimide, polypropylene, polyetherurethane, polycarbonateurethane and their copolymers. The heart sack and electrodes are very flexible and have good biocompliance with heart muscle. They have high strength and excellent mechanical properties. Ordinary pacemaker leads and defibrillation leads could be also imbedded into the heart sack to provide cardiac pacing or defibrillation. Electrical therapeutic heart sack devices are a new and noble concept. Cardiomyopathy is a commonly observed disease in an aging population. Cardiomyopathy is a defect of myocardial function. There are three categories of Cardiomyopathies; dilated cardiomyopathy, hypertrophic cardiomyopathy and restrictive cardiomyopathy. Dilated cardiomyopathy refers to a condition in which there is weakened contraction of the ventricles with an apparent dilation of the ventricles. This leads to inadequate perfusion, and increased pulmonary and systemic venous congestion. It will lead essentially to loss of heart function. The history of the disease is one of progressive deterioration. The mortality in one year is greater than 50% for those people who have a poorly functioning heart. Hyper cardiomyopathy is a disease of the heart muscle. It is characterized with an overactive left ventricle due to its increase in muscle mass resulting in an obstruction of the blood that is being pumped from the left ventricle to the rest of the body. This causes dyspnea on exertion and chest pain due to ischemia. Currently, there is no treatment to alter the course of the disease. Restrictive cardiomyopathy is least common of cardiomyopathies. It is due to other pathological processes such as scerderma, amyloid, sarcoid, or storage decease. This invention is to prevent enlargement of the heart and thinning of the heart wall of patients with dilated cardiomyopathy, or hypertrophic cardiomyopathy by the use of a heart sack. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Classification of supraventricular and ventricular cardiac rhythms using cross channel timing algorithm Inventor(s): Hsu, William; (Circle Pines, MN) Correspondence: Schwegman, Lundberg, Woessner & Kluth, P.A.; P.O. Box 2938; Minneapolis; MN; 55402; US Patent Application Number: 20030060849 Date filed: July 23, 2002 Abstract: A system and method for classifying cardiac complexes sensed during a tachycardia episode. A first cardiac signal and a second cardiac signal are sensed, where the first cardiac signal has a voltage. A first cardiac complex and a second cardiac complex of a cardiac cycle are detected in the first and second cardiac signal, respectively. A predetermined alignment feature is identified in the second cardiac complex. A datum is defined, or positioned, at a specified interval from the

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predetermined alignment feature of the second cardiac complex. Voltage values are then measured from the first cardiac complex at each of two or more measurement intervals from the datum. The voltage values are then compared voltage values measured from NSR cardiac complexes to classify the first cardiac complex is either a ventricular tachycardia complex or a supraventricular tachycardiac complex. Excerpt(s): This application is a division of U.S. patent application Ser. No. 09/352,056, filed Jul. 14, 1999, which is incorporated herein by reference. The subject matter relates generally to medical devices and more particularly to classification of sensed cardiac complexes. Effective, efficient ventricular pumping action depends on proper cardiac function. Proper cardiac function, in turn, relies on the synchronized contractions of the heart at regular intervals. When normal cardiac rhythm is initiated at the sinoatrial node, the heart is said to be in sinus rhythm. However, when the heart experiences irregularities in its coordinated contraction, due to electrophysiologic disturbances caused by a disease process or from an electrical disturbance, the heart is denoted to be arrhythmic. The resulting cardiac arrhythmia impairs cardiac efficiency and can be a potential life threatening event. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Cross chamber interval correlation Inventor(s): Hsu, William; (Circle Pines, MN), Sweeney, Robert J.; (Woodbury, MN) Correspondence: Schwegman, Lundberg, Woessner & Kluth, P.A.; P.O. Box 2938; Minneapolis; MN; 55402; US Patent Application Number: 20030109792 Date filed: January 21, 2003 Abstract: A system and method for discriminating cardiac rhythms occurring in an antegrade direction from cardiac rhythms occurring in a retrograde direction. Atrial and ventricular contractions are sensed, from which atrial and ventricular cycle lengths are determined. Ventricular contractions are also analyzed to determine the occurrence of a tachycardia episode that has a one-to-one association of atrial contractions to ventricular contractions. During a tachycardia episode having a one-to-one association of atrial contractions to ventricular contractions, the atrial cycle lengths are paired with the ventricular cycle lengths, where for each of the atrial cycle lengths the atrial cycle length is paired with at least one ventricular cycle length started before the first atrial contraction of each of the atrial cycle lengths and paired with at least one ventricular cycle length started after the first atrial contraction of each of the atrial cycle lengths. A retrograde correlation coefficient is then determined for the atrial cycle lengths paired with the ventricular cycle lengths started before the first atrial contraction, and an antegrade correlation coefficient is determined for the atrial cycle lengths paired with the ventricular cycle lengths started after the first atrial contraction. The tachycardiac episode is then classified based on a comparison of the antegrade correlation coefficient and the retrograde correlation coefficient. Excerpt(s): This application is a continuation of U.S. application Ser. No. 09/615,014, filed on Jul. 12, 2000, which is a division of U.S. application Ser. No. 09/283,159, filed on Apr. 1, 1999, now issued as U.S. Pat. No. 6,179,865, the specifications of which are hereby incorporated by reference. The present invention relates generally to implantable medical devices and more particularly to a system and method for discriminating cardiac rhythms occurring in an antegrade direction from cardiac rhythms occurring in

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a retrograde direction. The heart is generally divided into two chambers, the atrial chamber and the ventricular chamber. As the heart beats, the atrial chamber and the ventricular chamber of the heart go through a cardiac cycle. The cardiac cycle consists of one complete sequence of contraction and relaxation of the chambers of the heart. The terms systole and diastole are used to describe the contraction and relaxation phases the chambers of the heart experience during a cardiac cycle. In systole, the ventricular muscle cells are contracting to pump blood through the circulatory system. During diastole, the ventricular muscle cells relax, causing blood from the atrial chamber to fill the ventricular chamber. After the period of diastolic filling, the systolic phase of a new cardiac cycle is initiated. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Database of body surface ECG P wave integral maps for localization of left-sided atrial arrhythmias Inventor(s): Groenewegen, Arne Sippens; (Burlingame, CA), Mlynash, Michael D.; (Mountain View, CA) Correspondence: Marek Alboszta; Lumen Intellectual Property Services; 45 Cabot Avenue, Suite 110; Santa Clara; CA; 95051; US Patent Application Number: 20020026220 Date filed: August 1, 2001 Abstract: The present invention relates to classification and localization of arrhythmias. More specifically, a system and method is provided for developing a database of body surface ECG P wave maps for classification and localization of left-sided atrial arrhythmias. The invention includes generating and receiving P wave data in a subject by left atrial pacing or receiving P wave data in a subject during spontaneously occurring or induced left atrial arrhythmias; computing (e.g. potential or integral) maps of the P wave data; classifying the maps specific to a left atrial ectopic origin; verifying the classification procedure; averaging the classified maps into mean maps; and storing and accessing the mean maps in the database. The mean maps of the P wave data in the database can be used to automatically classify and localize P wave data from a patient obtained during a left atrial arrhythmia such as atrial tachycardia, focal atrial fibrillation or orthodromic atrioventricular reentrant tachycardia. Excerpt(s): This application is cross-referenced to and claims priority from U.S. application Ser. No. 09/809,719 filed Mar. 14, 2001, U.S. application Ser. No. 09/808,728 filed Mar. 14, 2001, provisional U.S. application Ser. No. 60/196,204 filed Apr. 11, 2000, and U.S. application Ser. No. 09/724,947 filed Nov. 28, 2000, all of which are incorporated herein by reference. This invention relates generally to a method for classification and localization of arrhythmias. More particularly, the present invention relates to a system for developing a database of body surface electrocardiogram (ECG) P wave data maps for localization of the origin of left-sided atrial arrhythmias. Early investigations utilizing atrial pacing in man to study the variations in scalar ECG morphology and vector loop of the P wave with varying sites of focal atrial origin, were primarily geared towards the differentiation of left- from right-sided atrial rhythms (e.g. Massumi R. A. and Tawakkol A. A. (1967), Direct study of left atrial P waves, Am. J. Cardiol. 20:331-340; and Harris B. C. et al. (1968) Left atrial rhythm; Experimental production in man, Circulation 37:1000-1014). Despite several attempts to develop a set of morphologic ECG criteria specific to a left-sided origin of an ectopic atrial rhythm, different algorithms were proposed and consensus appeared difficult to attain.

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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Defibrillation system Inventor(s): Fincke, Randall W.; (Winchester, MA), O'Leary, James P.; (Meford, MA), Owen, James M.; (Waltham, MA), Totman, Mark H.; (Winchester, MA) Correspondence: Gottlieb Rackman & Reisman PC; 270 Madison Avenue; 8th Floor; New York; NY; 100160601 Patent Application Number: 20030004547 Date filed: August 21, 2002 Abstract: A method of treating a patient for ventricular tachycardia using a wearable defibrillator includes monitoring the patient for a predetermined condition via one or more electrodes on the defibrillator, sending a message to the patient in response to the predetermined condition, activating the defibrillator so that the defibrillator delivers defibrillation energy to the patient, and storing at least one of the results of the monitoring, sending and activating steps in a memory on the defibrillator. The method also includes downloading information stored in the memory of the defibrillator to a base station having an external interface, and transmitting the information downloaded from the memory of the base station to an external location via the external interface of the base station. Excerpt(s): The present invention is directed to a defibrillation device, and more particularly to a personal wearable pacer/cardioverter/defibrillator which monitors a patient's condition, detects shockable or paceable arrhythmias, determines consciousness, and, in the case that the patient is determined to be unconscious, administers therapy to the patient. Cardiac arrhythmias, such as ventricular fibrillation and ventricular tachycardia, are electrical malfunctions of the heart, in which regular electrical impulses in the heart are replaced by irregular, rapid impulses. These irregular, rapid impulses can cause the heart to stop normal contractions, thereby interrupting blood flow therethrough. Such an interruption in blood flow can cause organ damage or even death. Normal heart contractions, and thus normal blood flow, can be restored to a patient through application of electric shock. This procedure, which is called defibrillation, has proven highly effective at treating patients with cardiac arrhythmias, provided that it is administered within minutes of the arrhythmia. In the past, this was not always possible, since defibrillation units were large, and thus not easy to move, and could only be operated by an experienced clinician. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Device wtih redetection therapy thereshold Inventor(s): Nigam, Indra B.; (Tigard, OR), Shekhar, Mrigank; (Vancouver, WA), Thong, Tran; (Portland, OR) Correspondence: Hahn Loeser & Parks, Llp; Twin Oaks Estate; 1225 W. Market Street; Akron; OH; 44313; US Patent Application Number: 20040059390 Date filed: September 18, 2003

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Abstract: An arrangement for treating rhythm disturbances of a heart (H), especially tachycardia and fibrillation, has a device (FD) for detecting the heart rhythm and determining when a fibrillation threshold limit is exceeded and a therapy device or stimulator (IG). The therapy device (IG) is connected to the heart rhythm detecting device (FD), to begin to treat the fibrillation when the fibrillation threshold limit is exceeded. The heart rhythm detecting device determines whether a redetection threshold limit is still exceeded after the therapy device has treated the fibrillation, the redetection threshold limit being lower than the fibrillation threshold limit and higher than a tachycardia threshold limit. The therapy device continues to treat the fibrillation as long as the heart rhythm detector determines that the redection threshold limit is exceeded. Excerpt(s): This application claims the benefit of U.S. Provisional Application Serial No. 60/411,905 which is hereby incorporated herein by reference. The present invention relates to an device for treating cardiac arrthythmias and fibrillation. Particularly, the device relates to an implantable cardioverter/defibrillator having the capacity to provide redetection therapy. Cardiac tachycardia is heart rate, high compared to the normal rate, that provides inadequate pumping when compared to a normal healthy heart rhythm. Cardiac fibrillation is an even higher heart rate, where no coordinated heart contraction occurs, rendering the situation life-threatening. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Discrimination of atrial fibrillations for an active implantable medical device, in particular a defibrillator/cardiovertor Inventor(s): Henry, Christine; (Paris, FR), Limousin, Marcel; (Paris, FR) Correspondence: Orrick, Herrington & Sutcliffe Llp; 666 Fifth Avenue; New York; NY; 10103-0001; US Patent Application Number: 20020169483 Date filed: November 27, 2001 Abstract: An active implantable medical device, in particular a defibrillator/cardioverter, with a sophisticated discrimination of atrial fibrillations. This device is able to deliver therapy for defibrillation, cardioversion, and/or ventricular and/or atrial antitachycardiac pacing stimulation; sense the ventricular and atrial activity; identify a suspicion of and confirm the presence of episodes of tachycardia in the activity thus sensed; analyze the stability of detected RR intervals and the stability of the associated PR intervals; and, in the event of a detection of stable RR intervals and unstable PR intervals, discriminate between atrial fibrillation with fast ventricular rhythm and atrial fibrillation with ventricular tachycardia, and to control delivery of a differentiated therapy according to one case or the other. A bi-tachycardia discrimination also can be made. Excerpt(s): The present invention is directed to "active implantable medical devices" as such devices are defined by the Jun. 20, 1990 directive 90/385/CEE of the Council of the European Communities, and more particularly to the family of devices that are able to deliver to the heart pulses of high energy (i.e., an energy level notably exceeding the energy level provided for conventional pacing stimulation) in order to terminate a tachyarrythmia. Such devices also typically include a programmed therapy mode of stimulation at high frequency or Anti-Tachycardia Pacing ("ATP"). These devices are commonly called "implantable defibrillators" or "implantable cardiovertors". It should,

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however, be understood that the invention also covers implantable defibrillator/cardiovertor/pacemaker and implantable defibrillator/pacemaker devices. The high energy shock must be delivered when a ventricular tachycardia (VT) is detected, provided that the condition detected as a VT condition is indeed a true VT condition, and not a supraventricular tachycardia (SVT) condition (or some other condition). Indeed, in the case of an SVT condition, the tachycardia is of an atrial origin and the therapy shock that would be delivered would be without effect because the electrode that delivers the defibrillation therapy or, if necessary, the stimulation (ATP) therapy, is not located in the atrium. Actually, these situations cover various forms of a heartbeat rate disorder: When in the presence of an abnormally fast heartbeat rate (i.e., a tachyarrhythmia), this disorder can be caused by a ventricular fibrillation (VF), a ventricular tachycardia (VT), a sinusal tachycardia (ST) or a supraventricular tachycardia (SVT). A supraventricular tachycardia disorder condition covers atrial tachycardia, atrial flutter and atrial fibrillation (AF). Heart beat rate disorders can exist simultaneously, and in such case one speaks about "bi-tachycardia," in particular, for example, the presence of an atrial fibrillaton combined with a ventricular tachycardia. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

DYNAMIC NON-COMPETITIVE ATRIAL PACING Inventor(s): Betzold, Robert A.; (Fridley, MN), Sheth, Nirav Vijay; (Coon Rapids, MN) Correspondence: Medtronic, INC.; 710 Medtronic Parkway NE; Ms-lc340; Minneapolis; MN; 55432-5604; US Patent Application Number: 20030036777 Date filed: August 14, 2001 Abstract: The invention is directed to pacing techniques designed to avoid competitive atrial pacing. In particular, the techniques dynamically adjust a non-competitive atrial pacing (NCAP) interval based on sensed cardiac conditions. An apparatus capable of delivering pacing stimuli, such as a pacemaker or an implantable cardioverter/defibrillator (ICD), is described that inhibits delivery of an atrial pacing stimulus for an NCAP interval having a duration that is adjusted according to sensed cardiac conditions. The apparatus may adjust the duration of the NCAP interval when sensing, for example, premature ventricular contraction (PVC), pacemaker mediated tachycardia (PMT), or atrial arrhythmia (AA). Excerpt(s): The invention relates to medical devices, and more particularly, to medical devices that deliver pacing stimuli to a heart. A pacemaker is an electronic medical device that is used to selectively stimulate a heart with electrical pulses in order to assist the heart in circulating blood. A pacemaker may be an external device connected to the body using electrodes, but more commonly is an implanted device operating from internal batteries or via an inductive link to an external power source. Depending upon the disease or malfunction of the heart, the pacemaker delivers pacing pulses to the atrium, the ventricles, or both, in the case of dual chamber pacemakers. By monitoring electrical activity sensed from the heart, the pacemaker determines the intrinsic rhythm of the heart, and provides stimulation pulses that force depolarization of the atrium, ventricles, or both, at appropriate times to stabilize the electrical rhythm of the heart. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Galenical preparations of dapsone and related sulphones, and method of therapeutic and preventative treatment of disease Inventor(s): Aberg, A K Gunnar; (Sarasota, FL), Bain, Allen I; (Vancouver, CA), Zolotoy, Alexander; (Richmond, CA) Correspondence: Kevin S Lemack; Neilds & Lemack; 176 E Main Street; Westboro; MA; 01581; US Patent Application Number: 20030092635 Date filed: August 26, 2002 Abstract: Dapsone and related sulfones are known to have therapeutic activity against leprosy, dermatitis herpetiformis, actinomycotic mycetoma, asthma, malaria, rheumatoid arthritis, Kaposis sarcoma, pneumocystis carini (pneumonia), subcorneal pustular dermatosis and cystic acne, in patients in need of such therapy. These sulfones are also known to have therapeutic activity against memory loss in patients in need of such therapy, including patients suffering from Alzheimer's disease and related neurodegenerative disorders. It has now been found that new, modified-release formulations of dapsone and related sulfones may also be used that decrease side effects and increase effectiveness of the drugs. New methods are disclosed utilizing certain formulations of dapsone and related sulfones that improve the therapeutic index of said drugs. Side effects of these drugs are known to those skilled in the art and include, but are not restricted to anorexia, psychosis, agranulocytosis, peripheral neuritis, hemolysis, methemoglobinemia, nausea, vomiting, headache, dizziness, tachycardia, nervousness, insomnia and skin disorders. Modified-release (as defined herein) formulations of dapsone have now been found to avoid some or all of these side effects, and to have more efficacy on potency. Excerpt(s): The object of the present invention pertains to a method of treating or preventing certain diseases in a human being while increasing compliance, reducing side effects and improving efficacy of the active therapeutic ingredient(s) within a large therapeutic range. The method comprises the use of modified-release dosage formulations of sulfone compounds including 4,4'-diaminodiphenylsulfone, its didextrose sulfonate derivative(s), their analogs, metabolites, any enantiomers, any diasteriomers, or mixtures thereof and/or therapeutically acceptable salts thereof. Dapsone is an active substance that is known in the treatment of various infectious diseases and inflammatory conditions. There is a wealth of data and experimental studies regarding the activity of dapsone and related sulfones. In particular, there is a large amount of data regarding the bioavailability and pharmacokinetics of the drug. It is also known in the prior art that dapsone has therapeutic activity against leprosy, dermatitis herpetiformis, actinomycotic mycetoma, asthma, malaria, rheumatoid arthritis, Kaposis sarcoma, pneumocystis carinii (pneumonia), subcorneal pustular dermatosis and cystic acne, in patients in need of such therapy. However, since the acute or chronic toxicity of dapsone is unacceptable at the doses necessary to treat most diseases, it is not possible to use this compound for these indications in the presently available formulation(s). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Implantable device for diagnosing and distinguishing supraventricular and ventricular tachycardias Inventor(s): Schauerte, Patrick; (Herzogenrath, DE) Correspondence: Stephen L. Grant; Oldham & Oldham CO., L.P.A.; Twin Oaks Estate; 1225 West Market Street; Akron; OH; 44313-7188; US Patent Application Number: 20020035335 Date filed: November 30, 2000 Abstract: An implantable device for diagnosing and distinguishing supraventricular and ventricular tachycardias includes electrodes for stimulating parasympathetic nerves of the atrioventricular and/or sinus node; electrodes for stimulating the atria and ventricles and/or for ventricular cardioversion/defibrillation; a device for producing electrical parasympathetic stimulation pulses passed to the electrodes; a device for detecting the atrial and/or ventricular rate, by ascertaining a time interval between atrial and/or ventricular depolarization; a device for programming a frequency limit above which a rate of the ventricles is recognized as tachycardia; a comparison device for comparing the measured heart rate during parasympathetic stimulation to the heart rate prior to or without parasympathetic stimulation and/or to the frequency limit, which delivers an output signal when with parasympathetic stimulation the heart rate falls below the comparison value by more than a predetermined amount; and an inhibition unit which responds to the output signal to inhibit ventricular myocardial over-stimulation therapy. Excerpt(s): The invention concerns an implantable device for diagnosing and distinguishing supraventricular and ventricular tachycardias. In a healthy human, a rhythmic cardiac action is predetermined by a natural pacemaker in the so-called sinus node. That electrical pulse is passed by way of the atria of the heart to the atrioventricular node, by way of which excitation of the main chambers or ventricles of the heart is implemented. A rise in the heart rate of over 100 beats per minute is referred to as tachycardia. Under conditions of physical stress, there is a rise in the sinus node frequency which is transmitted by way of the atrioventricular node to the ventricles (sinus tachycardia). In many humans there is no sinus rhythm but the atria are excited electrically quickly and regularly (atrial tachycardia) or completely irregularly and quickly (so-called atrial fibrillation=AF). That situation can involve very fast transmission of the electrical atrial pulses to the ventricles. AF is the most frequent disturbance in cardiac rhythm in a human being. AF occurs with increasing age and is to be encountered in about 4% of people who are over 60 years old and 10% of people who are over 75 years old. Besides these so-called "benign" (atrial) tachycardias which cannot result in cardiac arrest, there are also so-called "malign" tachycardias which have their origin primarily in the ventricles and which are in part transmitted in retrograde fashion by way of the atrioventricular node to the atria. By virtue of the contraction movements of the ventricles in the event of ventricular tachycardia, which are generally more adverse in contrast to atrial tachycardia, a loss of consciousness of the patient generally occurs quickly in situations involving ventricular tachycardias, or the ventricular tachycardia degenerates into ventricular fibrillation, which amounts to functional cardiac arrest. Ventricular tachycardias or ventricle fibrillation are also the cause of socalled sudden cardiac death which at the present time is the leading cause of death in the industrialized countries. Implantable cardioverter/defibrillators (ICD) can automatically terminate ventricle frequencies (ventricular tachycardias or ventricle fibrillation) which are life-threateningly fast, by virtue of ventricular over-stimulation or cardioversion/defibrillation. It could be shown that ICDs result in a significant

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prolongation of the survival rate of patients after having suffered a cardiovascular arrest and are in that respect clearly superior to drug therapy. Furthermore, ICDs also extend the life expectancy in the case of patients with restricted ventricular pump function (primary prophylaxis). The therapy (shock) delivery of ICDs occurs when the ventricle frequency exceeds a programmed limit value. In that respect, no consideration is initially given to whether the fast ventricle frequency is caused by a "benign" rise in the frequency of the atrias, which is not life-threatening (sinus tachycardias, atrial tachycardias or atrial fibrillation), or a life-threatening rise in the frequency of the ventricles. Therefore, many patients in which an ICD was implanted involve inadequate shock delivery in a situation involving supraventricular tachycardias. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method and apparatus for delaying a ventricular tachycardia therapy Inventor(s): Burnes, John E.; (Andover, MN), DeGroot, Paul J.; (Brooklyn Park, MN) Correspondence: Medtronic, INC.; 710 Medtronic Parkway NE; Ms-lc340; Minneapolis; MN; 55432-5604; US Patent Application Number: 20030204209 Date filed: April 26, 2002 Abstract: A device and method to detect slow ventricular tachycardia, deliver antitachycardia pacing therapies, and delay a scheduled shock therapy if the ventricular tachycardia is not terminated or accelerated. Preferably, a shock therapy is delayed after verifying hemodynamic stability based on a hemodynamic sensor. After a shock is delayed, the device operates in a high alert mode for redetecting an accelerated tachycardia. Anti-tachycardia pacing therapies are repeated during the shock delay. A number of conditions can trigger delivery of the delayed shock therapy including a specified period of elapsed time; determination that the patient is likely to be asleep; detection of myocardial ischemia; detection of compromised hemodynamics, or detection of a substantially prone position or sudden change in position. A delayed shock therapy may be triggered by the patient and repeated delivery of painful shock therapies in patients that are not seriously compromised by a recurring, slow ventricular tachycardia is avoided. Excerpt(s): The present invention relates to an implantable cardiac stimulation device capable of delivering anti-tachycardia therapy and more specifically a device and method for delaying shock therapies when a detected slow ventricular tachycardia is determined to be stable. Implantable medical devices are available for treating cardiac arrhythmias by delivering electrical shock therapy for cardioverting or defibrillating the heart in addition to cardiac pacing. Such a device, commonly known as an implantable cardioverter defibrillator or "ICD", senses a patient's heart rhythm and classifies the rhythm according to a number of rate zones in order to detect episodes of tachycardia or fibrillation. Single chamber devices are available for treating either atrial arrhythmias or ventricular arrhythmias, and dual chamber devices are available for treating both atrial and ventricular arrhythmias. Rate zone classifications typically include normal sinus rhythm, tachycardia, and fibrillation. In response to tachycardia detection, a number of tiered therapies may be delivered beginning with anti-tachycardia pacing therapies and escalating to more aggressive shock therapies until the tachycardia is terminated. Termination of a tachycardia is commonly referred to as "cardioversion." In modern implantable cardioverter defibrillators, the physician programs the particular therapies into the device ahead of time, and a menu of therapies is typically provided. For

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example, on initial detection of an atrial or ventricular tachycardia, an anti-tachycardia pacing therapy may be selected and delivered to the chamber, in which the tachycardia is diagnosed or to both chambers. On redetection of tachycardia, a more aggressive antitachycardia pacing therapy may be scheduled. If repeated attempts at anti-tachycardia pacing therapies fail, a higher energy cardioversion pulse may be selected. Therapies for tachycardia termination may also vary with the rate of the detected tachycardia, with the therapies increasing in aggressiveness as the rate of the detected tachycardia increases. For example, fewer attempts at anti-tachycardia pacing may be undertaken prior to delivery of cardioversion pulses if the rate of the detected tachycardia is above a preset threshold. For an overview of tachycardia detection and treatment therapies reference is made to U.S. Pat. No. 5,545,186 issued to Olson et al. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method and apparatus for displaying information retrieved from an implanted medical device Inventor(s): Blowers, Paul; (St. Paul, MN), Dirnberger, Denise; (Blaine, MN), Jamar, Pamela; (Plymouth, MN), Ousdigian, Kevin T.; (St. Paul, MN), Stone, Karen A.; (White Bear Lake, MN), Webb, James D.; (Maple Grove, MN) Correspondence: Girma Wolde-michael; Medtronic, INC., MS 301; 7000 Central Avenue NE; Minneapolis; MN; 55432; US Patent Application Number: 20020077561 Date filed: December 14, 2000 Abstract: A graphical user interface is provided controllably displaying information retrieved from an implantable device, such as a pacemaker. The graphical user interface is comprised of a first and second window. The first window is adapted to display data identifying a plurality of episodes recorded by the implantable device, wherein the data is comprised of a plurality of fields. One of the fields may be used to identify a type of episode, such as ventricular tachycardia (VT), atrial and ventricular tachycardia (A&V), atrial fibrillation (AF), atrial flutter (Afl), atrial tachycardia (AT), and premature atrial contraction (PAC). The second window is adapted to display data types, such as VT, A&V, AF, Afl, AT, and PAC, that may be present in the plurality of fields, wherein at least one of the data types may be selected to filter the episodes displayed in the first window and display those episodes having the selected data types. Excerpt(s): This invention relates generally to a method and apparatus for displaying data, and, more particularly, to a method and apparatus for displaying data related to cardiac episodes, which have been recorded by an implanted medical device. Since the introduction of the first implantable pacemakers in the 1960s, there have been considerable advancements in both the field of electronics and medicine, such that there is presently a wide assortment of commercially available body-implantable electronic medical devices. The class of implantable medical devices now includes pacemakers, implantable cardioverters, defibrillators, neural stimulators, and drug administering devices, among others. Today's state-of-the-art implantable medical devices are vastly more sophisticated and complex than early ones, capable of performing significantly more complex tasks. The therapeutic benefits of such devices have been well proven. As the functional sophistication and complexity of implantable medical device systems have increased over the years, it has become increasingly useful to include a system for facilitating communication between one implanted device and another implanted or external device, for example, a programming console, monitoring system, or the like.

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Shortly after the introduction of the earliest pacemakers, it became apparent that it would be desirable for physicians to non-invasively obtain information regarding the operational status of the implanted device, and/or to exercise at least some control over the device, e.g., to turn the device on or off or adjust the pacing rate, after implant. As new, more advanced features have been incorporated into implantable devices, it has been increasingly useful to convey correspondingly more information to/from the device relating to the selection and control of those features. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method and apparatus for electrically forcing cardiac output in an arrhythmia patient Inventor(s): Kroll, Kai; (Minneapolis, MN), Kroll, Mark W.; (Simi Valley, CA) Correspondence: Alicia Griffin Mills; Fredrikson & Byron, P.A.; 4000 Pillsbury Center; 200 South Sixth Street; Minneapolis; MN; 55402-1425; US Patent Application Number: 20040044373 Date filed: May 5, 2003 Abstract: An electrical method and apparatus for stimulating cardiac cells causing contraction to force hemodynamic output during fibrillation, hemodynamically compromising tachycardia, or asystole. Forcing fields are applied to the heart to give cardiac output on an emergency basis until the arrhythmia ceases or other intervention takes place. The device is used as a stand alone external or internal device, or as a backup to an ICD, atrial defibrillator, or an anti-tachycardia pacemaker. The method and apparatus maintain some cardiac output and not necessarily defibrillation. Excerpt(s): The invention relates to the field of therapies for cardiac arrhythmias, and more particularly, to a method and an apparatus for forcing cardiac output by delivering a pulsatile electrical field to the heart during fibrillation of a hemodynamically compromising tachycardia. Approximately 400,000 Americans succumb to ventricular fibrillation each year. It is known that ventricular fibrillation, a usually fatal heart arrhythmia, can only be terminated by the application of an electrical shock delivered to the heart. This is through electrodes applied to the chest connected to an external defibrillator or electrodes implanted within the body connected to an implantable cardioverter defibrillator (ICD). Paramedics cannot usually respond rapidly enough with their external defibrillators to restore life. New methods of dealing with this problem include less expensive external defibrillators (and thus more readily available) and smaller implantable defibrillators. Since the first use on humans of a completely implantable cardiac defibrillator in 1980, research has focused on making them continually smaller and more efficient by reducing the defibrillation threshold energy level. The goal has been to reduce the size of the implantable device so that it could be implanted prophylactically, I.E., in high risk patients before an episode of ventricular fibrillation. An ICD includes an electrical pulse generator and an arrhythmia detection circuit coupled to the heart by a series of two or more electrodes implanted in the body. A battery power supply, and one or more charge storage capacitors are used for delivering defibrillation shocks in the form of electrical current pulses to the heart. These devices try to restore normal rhythm from the fibrillation. While it works well at restoring normal function, the ICD is large in size and not practical for a truly prophylactic device. A small device capable of maintaining minimal cardiac output, in high risk patients, prior to admission into an emergency room is needed. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method and apparatus for implementing task-oriented induction capabilities in an implantable cardioverter defibrillator and programmer Inventor(s): Degroot, Paul J.; (Brooklyn Park, MN), Ericksen, James H.; (North Oaks, MN), Krause, Paul G.; (St. Louis Park, MN), Ousdigian, Kevin T.; (Shoreview, MN), Padmanabhan, Seema; (Maple Grove, MN), Willenbring, James E.; (St. Paul, MN) Correspondence: Medtronic, INC.; 710 Medtronic Parkway NE; Ms-lc340; Minneapolis; MN; 55432-5604; US Patent Application Number: 20030199927 Date filed: April 22, 2002 Abstract: The invention provides systems to prevent the delivery of anti-tachycardia pacing (ATP) following a defibrillation threshold (DFT) induction at implant. An algorithm that classifies episodes as induced or spontaneous is implemented, thereby enabling the ATP during charging feature to be operable only when spontaneous episodes are detected while temporarily suspending the ATP feature during the delivery of defibrillation shock after induction has been confirmed. Further, a user interface enables users to interact with an implantable medical device (IMD), particularly for setting a defibrillation threshold (DFT) or a 50 Hz burst from a single programmer screen. The user interface includes various functionalities to promote quick user access to parameters that govern diagnosis, therapy and other features of the IMD. A single screen enables the user to complete automatic and/or manual DFT inductions or a 50 Hz burst from a programmer interface while acquiring associated documentation from the same interface. Excerpt(s): This invention relates generally to the treatment of cardiac arrhythmias, and more particularly to a method and apparatus for inducing fibrillation. More particularly, the invention relates to performing all induction steps from one programmer screen without interaction with other tasks that could interfere with defibrillation threshold (DFT) testing. It has long been recognized that cardiac defibrillation can be accomplished through application of an electrical shock to the cardiac muscle. See, for example, Swartz et al., "Influence of T-Wave Shock Energy on Ventricular Fibrillation Vulnerability in Humans," Journal of American College of Cardiology, 1995 Conference Abstracts, February 1995; see also, Karolyi et al., "Timing of the T-Wave Shock for Inducing Ventricular Fibrillation in Patients With Implantable Cardioverter Defibrillators," PACE NASPE Abstracts, Vol. 18, April 1995 (Part II), p. 802. Numerous types of defibrillating devices, both external and implantable, are available for the purpose of cardiac defibrillation through electrical stimulation. One example of an implantable cardiac defibrillator (ICD) is the Medtronic.RTM. Gem.RTM. III DR, Model 7275 ICD, commercially available from the Assignee of the present invention. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method and apparatus for predicting recurring ventricular arrhythmias Inventor(s): Olson, Walter H.; (North Oaks, MN), Sharma, Vinod; (Roseville, MN), Zhou, Xiaohong; (Plymouth, MN) Correspondence: Medtronic, INC.; 710 Medtronic Parkway NE; Ms-lc340; Minneapolis; MN; 55432-5604; US Patent Application Number: 20030191403 Date filed: April 5, 2002

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Abstract: An implantable medical device and method are provided for assessing autonomic tone and risk factors associated with arrhythmias and, based on this assessment, an early recurrence of ventricular tachycardia or ventricular fibrillation is predicted. Specifically, changes in R-R interval, heart rate variability, patient activity, and myocardial ischemia are measured prior to and after a detected an arrhythmia episode. A recurrence score is calculated as a weighted sum of measured parameters and compared to a prediction criterion. The prediction criterion may be a preset threshold score or an individualized episode template based on previously calculated recurrence scores associated with recurring episodes. Stored parameters and episoderelated data may be downloaded for offline analyses for optimizing prediction criteria and monitoring patient status. Excerpt(s): The present invention relates to a medical device and, more specifically, to a device and method for assessing cardiac autonomic tone and predicting the early recurrence of ventricular tachycardia or fibrillation and triggering an alert system for initiation of possible preventive measures. Nearly all of detected arrhythmias appropriately treated by an ICD do not result in death. However, some patients with ICDs do experience fatal arrhythmias. Compromised hemodynamic output during a VT or VF episode can render a patient unconscious resulting in related serious injuries or death. Patients may experience recurrent VT or VF and be subjected to repeated shock therapies, which cause great discomfort. Because of the serious consequences of VT and VF, it is desirable to predict the occurrence of VT and VF so that an ICD can be prepared to immediately deliver a therapy or take preventive measures to prevent the occurrence. Prediction of an imminent VT or VF episode also enables preventive medical treatments to be delivered. A number of parameters for predicting a discreet VT or VF episode have been proposed including, for example, left ventricular dysfunction, myocardial ischemia, frequency of ventricular ectopic beats, heart rate variability, heart rate turbulence, or other electrocardiographic changes (see Shusterman et al., J Am Coll Cardiol. 1998;32:1891-9, and Schmidt et al., Lancet. 1999;353:1390-96). Changes in the autonomic nervous system are known contributing factors to arrhythmogenesis. The heart rate is normally regulated by a balance between the sympathetic and parasympathetic (vagal) components of the autonomic nervous system. Increased sympathetic activity, referred to as sympathetic tone, increases the heart rate and decreases heart rate variability. Increased vagal tone decreases the heart rate and increases heart rate variability. Heart rate variability (HRV) is the variation in consecutive heart rate cycles, which may be measured as ventricular cycle intervals, known as "R-R intervals," or as atrial cycle intervals, known as "A-A intervals." Changes in autonomic tone, especially in conjunction with myocardial ischemia, however, can play an important role in the development of arrhythmias. Therefore, indicators of changes in autonomic tone may be useful in predicting arrhythmias. Reference is made to U.S. Pat. No. 5,042,497 issued to Shapland. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method and apparatus for safely disabling runaway pacing protection in a cardiac rhythm management device Inventor(s): Baker, Kenneth L.; (Shoreview, MN), Ternes, David; (Roseville, MN) Correspondence: Nikolai & Mersereau, P.A.; 900 Second Avenue South; Suite 820; Minneapolis; MN; 55402; US Patent Application Number: 20030195573 Date filed: April 16, 2002

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Abstract: As a safety feature for a cardiac rhythm management device in which a runaway protection feature may be disabled to allow programmed electrical stimulation and/or burst pacing to evaluate the device's ability to rein in an induced episode of tachycardia, a circuit is provided to automatically re-enable the runaway protection feature not only upon a software fault being detected, but also upon the lapse of a predetermined time interval. Excerpt(s): This invention relates generally to cardiac rhythm management devices, including pacemakers and automatic implantable cardiac defibrillators, and more particularly to a safety feature that comes into play when it is desired to disable the runaway protection feature of such devices. For many years now, implantable cardiac pacers and pacer/defibrillators have incorporated a runaway protection capability that prevents the device from pacing the heart at an inordinately high rate due either to a software or a hardware fault. A runaway pacemaker is a pacemaker malfunction that may occur in single-chamber or multi-chamber pacing systems. It is usually the result of a minimum of at least two separate component failures within the pulse generator. The result is the rapid delivery of pacing stimuli to the heart, with the potential for inducing lethal arrhythmias, such as ventricular tachycardia or fibrillation. Newer devices incorporate a runaway protect circuit that prevents stimulation above a preset rate, typically between 180 and 200 bpm. Although somewhat rare, with modern pacing devices, this represents a medical emergency. Prompt surgical intervention to replace the device or, if all else fails, cutting the leads must be performed. This is most serious for a patient who may be pacemaker dependent. As those skilled in the art appreciate, in antitachycardia pacing, it is often desirable to apply high frequency bursts of stimulating pulses in an attempt to induce an episode of tachycardia so that the capabilities of the device in terminating the episode can be evaluated. This requires that the runaway protection logic of the device be disabled, thus allowing stimulation at rates above the runway protection limit. However, disabling the runaway protection feature of a cardiac rhythm management device is inherently unsafe to do. Should the firmware lose control of the process due to a hardware or a firmware fault, the device may operate without runaway protection for an indefinite amount of time. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method and system for automatic anti-tachycardia pacing Inventor(s): Girouard, Steven D.; (Woodbury, MN), Hahn, Stephen John; (Shoreview, MN), Zhu, Qingsheng; (Little Canada, MN) Correspondence: Schwegman, Lundberg, Woessner & Kluth, P.A.; P.O. Box 2938; Minneapolis; MN; 55402; US Patent Application Number: 20030083703 Date filed: October 25, 2001 Abstract: A method and system for delivering anti-tachycardia pacing is disclosed. A cardiac rhythm management device, such as an implantable pacemaker having antitachycardia pacing capability, delivers anti-tachycardia pacing therapy in accordance with an anti-tachycardia pacing protocol upon detection of a terminable arrhythmia. The anti-tachycardia pacing is delivered as a burst of one or more pacing pulses at a specified coupling interval after a sensed ventricular polarization. By sensing if an evoked potential occurs, the device can determine whether or not the anti-tachycardia pacing burst has captured the ventricle and can adjust the coupling interval and/or other parameters accordingly.

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Excerpt(s): This invention pertains to methods and system for treating cardiac arrhythmias with anti-tachycardia pacing. Tachyarrhythmias are abnormal heart rhythms characterized by a rapid heart rate, typically expressed in units of beats per minute (bpm). Examples of tachyarrhythmias include supraventricular tachycardias (SVT's) such as sinus tachycardia, atrial tachycardia, and atrial fibrillation. The most dangerous tachyarrythmias, however, are ventricular tachycardia (VT) and ventricular fibrillation (VF). Ventricular rhythms occur when re-entry of a depolarizing wavefront in areas of the ventricular myocardium with different conduction characteristics becomes self-sustaining or when an excitatory focus in the ventricle usurps control of the heart rate from the sinoatrial node. The result is rapid and irregular contraction of the ventricles out of electromechanical synchrony with the atria. Most ventricular rhythms exhibit an abnormal QRS complex in an electrocardiogram because they do not use the normal ventricular conduction system, the depolarization spreading instead from the excitatory focus or point of re-entry directly into the myocardium. Ventricular tachycardia is typically characterized by distorted QRS complexes that occur at a rapid rate, while ventricular fibrillation is diagnosed when the ventricle depolarizes in a chaotic fashion with QRS complexes of constantly changing shape. Both ventricular tachycardia and ventricular fibrillation are hemodynamically compromising, and both can be lifethreatening. Ventricular fibrillation, however, causes circulatory arrest within seconds and is the most common cause of sudden cardiac death. Cardioversion (an electrical shock delivered to the heart synchronously with the QRS complex) and defibrillation (an electrical shock delivered without synchronization to the QRS complex to terminate ventricular fibrillation) can be used to terminate most tachyarrhythmias, including SVT's, VT, and VF. The electric shock terminates the tachyarrhythmia by depolarizing all of the myocardium simultaneously and rendering it refractory. A class of cardiac rhythm management devices known as an implantable cardioverter/defibrillator (ICD) provides this kind of therapy by delivering a shock pulse to the heart when the device detects fibrillation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method and system for treatment of tachycardia and fibrillation Inventor(s): Mest, Robert A.; (Long Beach, CA) Correspondence: Christie, Parker & Hale, Llp; 350 West Colorado Boulevard; Suite 500; Pasadena; CA; 91105; US Patent Application Number: 20020120304 Date filed: February 28, 2001 Abstract: A method for regulating the heart rate of a patient comprises inserting into a blood vessel of the patient a catheter having an electrode assembly at its distal end. The electrode assembly comprises a generally circular main region that is generally transverse to the axis of the catheter and on which is mounted at least one electrode. The catheter is directed to an intravascular location wherein the at least one electrode on the electrode assembly is adjacent a selected cardiac sympathetic or parasympathetic nerve. The at least one electrode is stabilized at the intravascular location. A stimulus is delivered through the at least one electrode, the stimulus selected to stimulate the adjacent sympathetic or parasympathetic nerve to thereby cause a regulation of the patient's heart rate. Excerpt(s): The present invention relates to an improved method and system for treating and controlling tachycardia and arrhythmias, and more particularly treating and

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controlling atrial fibrillation and ventricular tachycardia. Tachycardia is the rapid beating of the heart caused by abnormalities in any part of the heart, for example the atria, Purkinje system, or ventricles. Often the extremely rapid beating of the heart is uncoordinated and leads to fibrillation or flutter. These conditions occur after myocardial infarctions, for example, or in various pathological conditions, such as a dilated heart or blockage of the Purkinje system. The conditions can also occur following chemical therapies (e.g., epinephrine) or repetitive stimulation. Atrial flutter often becomes atrial fibrillation within a few days or weeks and leads to a complete failure of the atria to pump blood. Atrial fibrillation is the most frequent tachycardia in patients. It most frequently occurs in patients over the age of 60 years and affects over 8% of patients with cardiovascular disease and people older than 80 years. Chronic atrial fibrillation doubles mortality, mostly due to an increased risk of stroke as well as other cardiovascular complications. Congestive heart disease imposes the highest risk for developing atrial fibrillation. Therefore, restoration of normal sinus rhythm by pharmacological or electrical cardioversion is attempted in many patients with atrial fibrillation. Unfortunately atrial fibrillation recurrence rates one year after successful cardioversion are high (75% without antiarrhythmic drug prophylaxis and 50% with aggressive antiarrhythmic medication). Moreover, the likelihood of cardioversion success is low in patients with chronic atrial fibrillation lasting longer than 2 years or in patients who have enlarged atria. In many of these patients, therapy is directed toward ventricular rate control during atrial fibrillation in order to stabilize cardiac function. However, in patients with concomitant heart failure, drugs that slow the ventricular rate during atrial fibrillation may further depress ventricular contractility and cause arterial hypotension or be of limited use due to side effects. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method of early detection of duchenne muscular dystrophy and other neuromuscular disease Inventor(s): Hampton, Thomas G.; (Framingham, MA) Correspondence: Lahive & Cockfield; 28 State Street; Boston; MA; 02109; US Patent Application Number: 20030003052 Date filed: June 19, 2002 Abstract: The mdx mouse is a model of Duchenne muscular dystrophy. The present invention describes that mdx mice exhibited clinically relevant cardiac phenotypes. A non-invasive method of recording electrocardiograms (ECGs) was used to a study mdx mice (n=15) and control mice (n=15). The mdx mice had significant tachycardia, consistent with observations in patients with muscular dystrophy. Heart-rate was nearly 15% faster in mdx mice than control mice (P<0.01). ECGs revealed significant shortening of the rate-corrected QT interval duration (QTc) in mdx mice compared to control mice (P<0.05). PR interval duration were shorter at baseline in mdx compared to control mice (P<0.05). The muscarinic antagonist atropine significantly increased heart-rate and decreased PR interval duration in C57 mice. Paradoxically, atropine significantly decreased heart-rate and increased PR interval duration in all mdx mice. Pharmacological autonomic blockade and baroreflex sensitivity testing demonstrated an imbalance in autonomic nervous system modulation of heart-rate, with decreased parasympathetic activity and increased sympathetic activity in mdx mice. These electrocardiographic findings in dystrophin-deficient mice provide new bases for diagnosing, understanding, and treating patients with Duchenne muscular dystrophy.

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Excerpt(s): This application claims priority to U.S. provisional patent application serial No. 60/299,302, filed Jun. 19, 2001, and to U.S. provisional patent application serial No. 60/338,821, filed Nov. 17, 2001. The contents of these provisional patent applications are incorporated herein by reference in their entirety. Dysfunction of the autonomic nervous system is an under-recognized but important aspect of the etiological and clinical manifestation of neuromuscular disorder such as Duchenne muscular dystrophy (DMD). DMD is an X-linked inherited disorder that affects over nearly 30 out of every 100,000 boys born in the United States. The disorder results from a defect in the gene for an enormous protein called dystrophin, which forms part of the scaffold in muscle fibers. Although the disorder is present from the initial stages of fetal development, there is no physical indication at birth that the baby is abnormal. Rarely is there physical diagnosis in the first year of life. Problems are usually not evident until 18 months to 4 years of age. Usually diagnosis is not made until the child is five. Nearly 50% of affected boys do not walk until 18 months of age or later. Duchenne children have difficulty climbing and getting up from the floor. Parents often comment that their child falls frequently. By the age 3 to 5 years, generalized muscle weakness becomes more obvious. Parents may be falsely encouraged by a seeming improvement at school age, but this may be due to natural growth and development. Weakness progresses rapidly after age 8 or 9, resulting in the inability to walk or stand unassisted. Leg braces may make walking possible for a year or two, but by early adolescence walking becomes impossible. There are some boys with Duchenne muscular dystrophy who have problems with delay in mental or language development. Eventually all the major muscles are affected. Lung capacity may decrease, resulting in an increased susceptibility to respiratory infections. Cardiac and respiratory failure are common in Duchenne patients. Autonomic nervous system abnormalities have now been frequently reported in patients. The cardiac phenotype includes decreased parasympathetic nervous activity and increased sympathetic nervous activity. Currently there is no reliable mode of prenatal diagnosis or cure. For a series of reasons, diagnosis of Duchenne patients using DNA markers from amniocytes is error ridden and deletion mutants are detectable in only 65% of cases. Therefore, early detection of the disease before locomotor or autonomic disturbances reduce quality of life or irreversibly affect outcome of the disease could significantly improve life-quality prospects and longevity in those afflicted with dystrophin-deficiency related diseases. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method of treating arrhythmias Inventor(s): Antzelevitch, Charles; (New Hartford, NY), Belardinelli, Luiz; (Menlo Park, CA), Blackburn, Brent; (Los Altos, CA) Correspondence: Pauline Ann Clarke; CV Therapeutics, INC.; 3172 Porter Drive; Palo Alto; CA; 94304; US Patent Application Number: 20030220344 Date filed: April 3, 2003 Abstract: Methods are provided for treating arrhythmias including tachycardias, such as idiopathic ventricular tachycardia, ventricular fibrillation, and Torsade de Pointes (TdP) in a manner that minimizes undesirable side effects. Excerpt(s): Priority is claimed to U.S. Provisional Patent Application Serial No. 60/370,150, filed Apr. 4, 2002, U.S. Provisional Patent Application Serial No. 60/408,292, filed Sep. 5, 2002, and U.S. Provisional Patent Application Serial No. 60/422,589, filed

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Oct. 30, 2002, the complete disclosures of which are hereby incorporated by reference. This invention relates to a method of treating cardiac arrhythmias, comprising administration of compounds that modulate the activity of specific cardiac ion channels while minimizing undesirable side effects. The heart is, in essence, a pump that is responsible for circulating blood throughout the body. In a normally functioning heart such circulation is caused by the generation of electrical impulses that, for example, increase or decrease the heart rate and/or the force of contraction in response to the demands of the circulatory system. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods for adjusting cardiac detection criteria and implantable medical devices using same Inventor(s): Ferek-Petric, Bozidar; (Zagreb, HR) Correspondence: Medtronic, INC.; 710 Medtronic Parkway NE; Ms-lc340; Minneapolis; MN; 55432-5604; US Patent Application Number: 20020188215 Date filed: April 30, 2001 Abstract: Implantable medical devices and methods of tachycardia detection that provide adjustable detection criteria based upon a hemodynamic parameter. In some embodiments, the apparatus and methods provide for detection and delivery of therapy for hemodynamically stable and hemodynamically unstable tachycardias by varying a number of intervals detected (NID) threshold based on hemodynamic measurements. Excerpt(s): The present invention relates to implantable medical devices and methods for cardiac stimulation. More particularly, the present invention pertains to implantable medical devices and methods that employ adjustable detection criteria. Implantable medical devices, such as pacing apparatus, generally include detection algorithms to detect various types of heart conditions, e.g., ventricular fibrillation (VF), ventricular tachycardia (VT), supra-ventricular tachyarrhythmia (SVT), etc., that require employment of therapy. For example, detection algorithms may be based on heart rate, or in other words R-R intervals, alone or in combination with other additional criteria, such as sudden onset criteria, rate stability criteria, and QRS width. For example, dual chamber pacemaker-cardioverter-defibrillators (PCDs) may be able to differentiate supra-ventricular tachyarrhythmias from ventricular tachycardias using an algorithm that processes atrial and/or ventricular EGM signals. In many cases, to increase detection accuracy and/or to distinguish various types of arrhythmias, such as various types of ventricular tachyarrhythmias, devices may include a type of hemodynamic sensor, e.g., an intra-cardial blood pressure sensor and/or a flow sensor. A common approach to programming PCDs uses the specification of discrete heart rate zones (e.g., R-R interval zones) for ventricular fibrillation (VF) and various types of ventricular tachycardia (VT). Each rate zone for the detection algorithms, for example, may be defined using different heart rates and, correspondingly, different R-R interval values. For example, a PCD may have three different heart rate zones: VT, fast VT, and VF. Each of these rate zones, e.g., VT, fast VT, and VF, may be treated by a separately defined therapy. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Partial and full agonists of A1 adenosine receptors Inventor(s): Elzein, Elfatih; (Fremont, CA), Ibrahim, Prabha; (Mountain View, CA), Palle, Venkata; (Sunnyvale, CA), Varkhedkar, Vaibhav; (Mountain View, CA), Zablocki, Jeff; (Mountain View, CA) Correspondence: Brian Lewis; CV Therapeutics, INC.; 3172 Porter Drive; Palo Alto; CA; 94304; US Patent Application Number: 20030050275 Date filed: July 11, 2002 Abstract: Disclosed are novel compounds that are partial and full A.sub.1 adenosine receptor agonists, useful for treating various disease states, in particular tachycardia and atrial flutter, angina, and myocardial infarction. Excerpt(s): The present invention relates to novel compounds that are partial or full A.sub.1 adenosine receptor agonists, and to their use in treating mammals for various disease states, including modifying cardiac activity, in particular treatment of arrhythmia. The compounds are also useful for treating CNS disorders, diabetic disorders, obesity, and modifying adipocyte function. The invention also relates to methods for their preparation, and to pharmaceutical compositions containing such compounds. Adenosine is a naturally occurring nucleoside, which exerts its biological effects by interacting with a family of adenosine receptors known as A.sub.1, A.sub.2a, A.sub.2b, and A.sub.3, all of which modulate important physiological processes. For example, A.sub.2A adenosine receptors modulate coronary vasodilation, A.sub.2B receptors have been implicated in mast cell activation, asthma, vasodilation, regulation of cell growth, intestinal function, and modulation of neurosecretion (See Adenosine A.sub.2B Receptors as Therapeutic Targets, Drug Dev Res 45:198; Feoktistov et al., Trends Pharmacol Sci 19:148-153), and A.sub.3 adenosine receptors modulate cell proliferation processes. The A.sub.1 adenosine receptor mediates two distinct physiological responses. Inhibition of the cardiostimulatory effects of catecholamine is mediated via the inhibition of adenylate cyclase, whereas the direct effects to slow the heart rate (HR) and to prolong impulse propagation through the AV node are due in great part to activation of I.sub.KAdo. (B. Lerman and L. Belardinelli Circulation, Vol. 83 (1991), P 1499-1509 and J. C. Shryock and L. Belardinelli The Am. J. Cardiology, Vol. 79 (1997) P 2-10). Stimulation of the A.sub.1 adenosine receptor shortens the duration and decreases the amplitude of the action potential of AV nodal cells, and hence prolongs the refractory period of the AV nodal cell. Thus, stimulation of A.sub.1 receptors provides a method of treating supraventricular tachycardias, including termination of nodal re-entrant tachycardias, and control of ventricular rate during atrial fibrillation and flutter. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Substituted dicinnamoylquinides and their use in Augmentation of adenosine function Inventor(s): Lovinger, David M.; (Rockville, TN), Martin, Peter R.; (Nashville, TN), Paulis, Tomas de; (Hermitage, TN) Correspondence: Douglas W. Schelling, PH.D.; Waddey & Patterson; Bank OF America Plaza; 414 Union Street, Suite 2020; Nashville; TN; 37219; US Patent Application Number: 20030013758 Date filed: May 10, 2002 Abstract: This invention describes the novel use of alkyl, alkoxyl, halogenyl, or hydroxy substituted dicinnamoylquinides as therapeutic agents for enhancing adenosine levels in the brain and peripheral organs. These agents are particularly useful in treating human diseases or conditions that benefit from acute or chronic elevated levels of adenosine, such as reperfusion injury, coronary or cerebral ischemia, coronary vasoconstriction, paroxysmal supraventricular tachycardia, hypertension, wound healing, diabetes, inflammation, or sleep disturbances. They can also be used to protect normal cells from chemotoxicity in patients undergoing cancer therapy, and reverse the behavioral effects of caffeine intake. Excerpt(s): The present invention relates generally to the field of use of alkyl, alkoxyl, halogenyl, or hydroxyl substituted dicinnamoylquinides. Specifically, the present invention relates to the use of the above-mentioned compounds to treat diseases or conditions that improve from either an acute or chronic increase in adenosine levels. Adenosine is a neuromodulator known to produce profound effects on blood flow, neurotransmission, cellular functions, and metabolism. Intracellular levels of adenosine are disclosed to be maintained by an active transport of adenosine across the cell membrane by means of a carrier-mediated, saturable nucleoside transporter, consisting of a 50 kDa protein in the form of a dimer (Thorn and Jarvis, Gen Pharmacol 27, 613-620 (1996)). This transporter protein is widely distributed in thalamic, cortical, and particularly in striatal neurons in the human brain (Glass et al, Brain Res 710, 79-91 (1996), Jennings et al, Neuropharmacol 40, 722-731 (2001)), where it regulates adenosinedopamine interactions (Dunwiddie and Masino, Ann Rev Neurosci 24, 31-55 (2001)). Of all mammals studied, the human transporter is disclosed to be one of the most sensitive to adenosine (Hammond, N-S Arch Pharmacol 361, 373-382 (2000)), resulting in an extremely short half-life of adenosine in blood. Inhibition of the adenosine transporter is disclosed to prevent the intracellular metabolism of adenosine and prolongs the presence of high levels of adenosine (Thorn and Jarvis, Gen Pharmacol 27, 613-620 (1996). This increased level of adenosine in brain causes stimulation of adenosine receptor subtypes, similar to the effects seen from unselective adenosine receptor agonizes. Activation of the adenosine A.sub.2B receptor was found to increase vascular endothelial growth factor production, resulting in angiogenic neovascularization (Grant et al, Circ Res 85, 699-706 (1999). Recent studies have demonstrated that agonists for the adenosine A.sub.3 receptor have antiinflammatory properties (Fishman et al, J. Cell Physiol 183, 393-398 (2000)). Both agonists at the adenosine A.sub.1 and A.sub.3 receptors have shown cardioprotective activity in man (Baraldi et al, Ed Res Rev 20, 103128 (2000)), and conjugate compounds of potent adenosine A.sub.1 and A.sub.3 receptor agonists have shown full cardioprotection in a myocyte model of ischemia (Jacobson et al, J. Biol Chem 275, 30272-30279 (2000)). Based on the discovery that certain naturally occurring 4-hydroxycinnamoyl di-esters of quinic acid gamma-lactone in roasted coffee (Hucke et al, Z. Lebensm Unters Forsch 180, 479-484 (1985)), but not in tea or any other caffeine containing beverages, inhibits the human adenosine transporter (de Pails et al,

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Eur J Pharmacol 442, 213-221 (2002)), the present invention provides, in part, methods of using 3,4-disubstituted cinnamoyl esters of quinic acid 1,5-lactone, exemplified by Formula 1, having no substituent, or a halogen atom or a hydroxyl, alkyl or alkoxyl group in either of the aromatic 3-, 4- and 5-positions to inhibit the human adenosine transporter. By inhibiting the adenosine transporter, the metabolism of intracellular adenosine is prevented resulting in increased levels of extracellular adenosine. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

System and method for arrhythmia discrimination Inventor(s): Hsu, William; (Circle Pines, MN), Smith, Joseph Martin; (St. Louis, MO) Correspondence: Schwegman, Lundberg, Woessner & Kluth, P.A.; P.O. Box 2938; Minneapolis; MN; 55402; US Patent Application Number: 20020091333 Date filed: October 22, 2001 Abstract: The present invention provides a system and a method for discriminating supraventricular tachyarrhythmias from ventricular arrhythmias during a tachycardia episode. First cardiac signals and second cardiac signals are sampled for cardiac complexes. A first feature on the first cardiac signal and a second feature on the second cardiac signal are utilized to determine an average time difference for a plurality of normal sinus rhythm complexes. A time difference between the first feature and the second feature is then determined for each cardiac complex of a tachycardiac rhythm. The cardiac complex is characterized as a ventricular tachycardia complex if the time difference exceeds the average time difference by a predetermined amount. Otherwise, it is classified as VT if its morphology after alignment is different from that during normal sinus rhythm. Excerpt(s): The subject matter relates generally to implantable medical devices and more particularly to arrhythmia discrimination with an implantable medical device. Effective, efficient ventricular pumping action depends on proper cardiac function. Proper cardiac function, in turn, relies on the synchronized contractions of the heart at regular intervals. When normal cardiac rhythm is initiated at the sinoatrial node, the heart is said to be in sinus rhythm. However, when the heart experiences irregularities in its coordinated contraction, due to electrophysiologic disturbances caused by a disease process or from an electrical disturbance, the heart is denoted to be arrhythmic. The resulting cardiac arrhythmia impairs cardiac efficiency and can be a potential life threatening event. Cardiac arrhythmias occurring in the atrial of the heart are called supraventricular tachyarrhythmias (SVTs). Cardiac arrhythmias occurring in the ventricular region of the heart are called ventricular tachyarrhythmias (VTs). SVTs and VTs are morphologically and physiologically distinct events. VTs take many forms, including ventricular fibrillation and ventricular tachycardia. Ventricular fibrillation is a condition denoted by extremely rapid, nonsynchronous contractions of the ventricles. This condition is fatal unless the heart is returned to sinus rhythm within a few minutes. Ventricular tachycardia are conditions denoted by a rapid heart beat, 150 to 250 beats per minute, that has its origin in some abnormal location within the ventricular myocardium. The abnormal location is typically results from damage to the ventricular myocardium from a myocardial infarction. Ventricular tachycardia can quickly degenerate into ventricular fibrillation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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System and method for determining reentrant ventricular tachycardia isthmus and shape for catheter ablation Inventor(s): Ciaccio, Edward J.; (Cherry Hill, NJ), Tosti, Alexis Christine; (Gladstone, NJ), Wit, Andrew L.; (Massapequa, NY) Correspondence: Cooper & Dunham, Llp; 1185 Avenue OF The Americas; New York; NY; 10036; US Patent Application Number: 20030023130 Date filed: July 30, 2001 Abstract: A method for identifying and localizing a reentrant circuit isthmus in a heart of a subject during sinus rhythm, including: a) receiving electrogram signals from the heart during sinus rhythm via electrodes; b) storing the electrogram signals; c) creating a map based on the electrogram signals; d) finding a center reference activation location on the map; e) defining measurement vectors originating from the center reference activation location; f) selecting from the measurement vectors a primary axis vector indicating a location of the reentrant circuit isthmus in the heart; g) finding threshold points of electrogram signals on the map; h) connecting the threshold points to form a polygon indicating a shape of the reentrant circuit isthmus in the heart. Excerpt(s): Throughout this disclosure, various publications may be referenced by Arabic numerals in brackets. Disclosures of these publications in their entireties are hereby incorporated by reference into this application to more fully describe the state of the art to which this disclosure pertains. Full citations of these publications may be found at the end of the specification. During ventricular tachycardia, the heart beats rapidly which can be debilitating to the patient and cause such things as tiredness and even syncope (i.e. fainting). This clinical problem usually follows a myocardial infarction (heart attack) and is caused by abnormal electrical conduction in the heart because the cells become damaged during the infarct. When conduction is slow and abnormal, a process called reentry can occur in which the propagating electrical wavefront travels in a circle, or double loop, and reenters the area where it had previously traveled. This propagation around the loop(s) occurs very rapidly, and a heartbeat occurs once each time the propagating wavefront traverses around the loop or loops. Since the condition is abnormal, the heart muscle does not contract as it should, so that the strength of the pumping action is reduced, and the rapidity of the heartbeat causes the heart chambers to not fill with blood completely. Therefore, because of both the poor filling action and the poor pumping action, there is less blood delivered to the tissues. This causes the maladies that the patient experiences. A promising cure for this ailment is radio-frequency catheter ablation, which does not require surgery and is permanent. In the ablation procedure, a catheter is inserted through an artery of the patient and is positioned in the heart chamber. At the appropriate location on the inner heart surface, known as the endocardium, radio-frequency energy is delivered from the tip of the catheter to the heart tissue, thereby blocking conduction at the place of delivery of the energy, which is called the target site on the heart. Ideally, energy is delivered to the location between the double loop where the electrical wavefront propagates. This is called the best, or optimal target site. However, it is sometimes difficult to locate the best target site, and also the precise surface area to which energy should be delivered is often unknown and presently must be done by trial and error. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Tachycardia rate hysteresis for dual-chambered cardiac stimulators Inventor(s): Armstrong, Randolph Kerry; (Missouri City, TX), Cook, Douglas Jason; (Minnetonka, MN) Correspondence: Schwegman, Lundberg, Woessner & Kluth, P.A.; P.O. Box 2938; Minneapolis; MN; 55402; US Patent Application Number: 20030088288 Date filed: December 16, 2002 Abstract: It has been determined that certain dual-chambered cardiac stimulators may operate in a region in which an atrial pacing event may obscure the detection of a ventricular tachyarrhythmia. Various exemplary techniques may be used to improve the ability of dual-chamber cardiac stimulators to detect such ventricular events. In accordance with one technique, it is determined whether a ventricular event should be classified as a ventricular tachyarrhythmia. If not, the VA interval is restarted as usual. However, if the ventricular event may be classified as a ventricular tachyarrhythmia, it is determined whether the ventricular event falls within the region in which an atrial pacing event may obscure its detection. If not, then the VA interval is restarted as usual. However, if the ventricular event falls within this region, the VA interval is restarted with the VT rate detection boundary. This has the effect of lengthening the VA interval and the AA interval in this region so that atrial pacing events will not obscure the sensing and treatment of ventricular tachyarrhythmias in the region. Excerpt(s): This application is a continuation of U.S. patent application Ser. No. 09/811,931, filed on Mar. 19, 2001, which is a division of U.S. patent application Ser. No. 09/332,781, filed on Jun. 14, 1999, now issued as U.S. Pat. No. 6,233,485, the specifications of which are hereby incorporated by reference. The present invention relates generally to cardiac stimulators and, more particularly, to dual-chamber cardiac stimulators that have an improved ability to detect tachyarrhythmias. As most people are aware, the human heart is an organ having four chambers. A septum divides the heart in half, with each half having two chambers. The upper chambers are referred to as the left and right atria, and the lower chambers are referred to as the left and right ventricles. Deoxygenated blood enters the right atrium through the pulmonary veins. Contraction of the right atrium and of the right ventricle pump the deoxygenated blood through the pulmonary arteries to the lungs where the blood is oxygenated. This oxygenated blood is carried to the left atrium by the pulmonary veins. From this cavity, the oxygenated blood passes to the left ventricle and is pumped to a large artery, the aorta, which delivers the pure blood to the other portions of the body through the various branches of the vascular system. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Vacuum coagulation probe for atrial fibrillation treatment Inventor(s): Whayne, James G.; (Chapel Hill, NC) Correspondence: James G. Whayne; 1200 Pinehurst DR.; Chapel Hill; NC; 27517; US Patent Application Number: 20030233090 Date filed: June 14, 2002 Abstract: An embodiment of the invention includes a surgical device for coagulating soft tissue such as atrial tissue in the treatment of atrial fibrillation, atrial flutter, and atrial

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tachycardia. The surgical device can include at least one elongate member comprising conductive elements adapted to coagulate soft tissue when radiofrequency or direct current energy is transmitted to the conductive elements. Openings through said conductive elements are routed through lumens in the elongate member to a vacuum source to actively engage the soft tissue surface intended to coagulate into intimate contact with the conductive elements to facilitate the coagulation process and ensure the lesions created are consistent, contiguous, and transmural. The embodiments of the invention can also incorporate cooling openings positioned near the conductive elements and coupled with a vacuum source or an injection source to transport fluid through the cooling openings causing the soft tissue surface to cool thus pushing the maximum temperature deeper into tissue. The embodiments of the invention can also incorporate features to tunnel between anatomic structures or dissect around the desired tissue surface to coagulate thereby enabling less invasive positioning of the soft tissue coagulating device and ensuring reliable and consistent heating of the soft tissue. Excerpt(s): Embodiments of the invention relate to devices and methods for less invasive treatment of atrial fibrillation. More particularly, certain embodiments of the invention relate to ablation and/or coagulation probes that utilize suction to ensure consistent and intimate tissue contact. These vacuum-assisted coagulation probes are capable of creating transmural, curvilinear lesions capable of preventing the propagation of wavelets that initiate and sustain atrial fibrillation, atrial flutter, or other arrhythmia substrate. The vacuum-assisted coagulation probes facilitate less invasive surgery involving thorascopic access and visualization to the target coagulation sites. Additionally, the vacuum-assisted coagulation probes of the invention are suitable for coagulating soft tissues (e.g. of the atria to treat atrial fibrillation, atrial flutter, or other arrhythmia) through a median sternotomy, lateral thoracotomy, intercostals port-access, mini-sternotomies, other less invasive approaches involving Xiphoid access, inguinal approaches, or sub-thoracic approaches adjacent the diaphram. Alternatively, the vacuum-assisted coagulation probes can be modified for catheter-based applications by elongating the shaft and altering the diameters and other feature dimensions for intravascular access. The vacuum-assisted coagulation probes can also be used to coagulate other soft tissues for cancer therapy in a wide-variety of applications (e.g. liver, prostate, colon, esophageal, gastrointestinal, gynecological, etc.), or shrinking of collagen in tissue structures such as skin, tendons, muscles, ligaments, vascular tissue during arthroscopic, laparoscopic, or other minimally invasive procedures. Certain embodiments of devices and methods of the invention also enable tunneling through and/or dissecting soft tissue structures by injecting fluid (air, CO.sub.2, saline, etc.) in high intensity streams that separate tissue structures by disrupting fatty deposits, ligaments, adventitial tissue, or other structure that holds anatomic structures together without damaging the anatomic structure the device is dissecting free or otherwise exposing. These devices of the invention enable less invasive access without having to manually dissect tissue structures to place the vacuum-assisted coagulation probes. As such, these fluid dissecting devices are capable of tunneling through the pulmonary veins, separate the pulmonary veins, the aorta, the pulmonary artery, and other anatomy from the atria to provide a path for the vacuum-assisted coagulation probe to directly appose the atrial epicardium throughout the desired length the lesion is expected to span, which is required to create transmural, curvilinear lesions. These embodiments may alternatively dissect other soft tissue structures during applications such as endoscopic saphenous vein harvesting, left internal mammary artery dissection, etc. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Keeping Current In order to stay informed about patents and patent applications dealing with tachycardia, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “tachycardia” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on tachycardia. You can also use this procedure to view pending patent applications concerning tachycardia. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 6. BOOKS ON TACHYCARDIA Overview This chapter provides bibliographic book references relating to tachycardia. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on tachycardia include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “tachycardia” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “tachycardia” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “tachycardia” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

An Electrophysiological Approach to the Diagnosis of Arrhythmias (Tachycardia Ser.: No 1) by Christopher R. Wyndham; ISBN: 0879935014; http://www.amazon.com/exec/obidos/ASIN/0879935014/icongroupinterna

•

Catheter Ablation of Ventricular Tachycardia in Patients with Structural Heart Disease,volume 13 by Martin Borggrefe, et al; ISBN: 0879934654; http://www.amazon.com/exec/obidos/ASIN/0879934654/icongroupinterna

•

Electrical stimulation of the heart in the study and treatment of tachycardias by Hein J. J. Wellens; ISBN: 0839106025; http://www.amazon.com/exec/obidos/ASIN/0839106025/icongroupinterna

•

Electrocardiographic Diagnosis of Tachycardias (Clinical Approaches to Tachyarrhythmias; V. 2) by Clifford J. Garratt, Michael J. Griffith; ISBN: 0879935987; http://www.amazon.com/exec/obidos/ASIN/0879935987/icongroupinterna

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•

Electrocardiography of Tachycardias by Niraj Varma, Vassillos P. Vassilikos; ISBN: 041248000X; http://www.amazon.com/exec/obidos/ASIN/041248000X/icongroupinterna

•

Management of ventricular tachycardia--role of mexiletine : proceedings of a symposium held in Copenhagen, Denmark, 25th-27th May, 1978; ISBN: 0444900594; http://www.amazon.com/exec/obidos/ASIN/0444900594/icongroupinterna

•

Pathophysiology of Tachycardia-Induced Heart Failure by Francis G. Spinale (Editor); ISBN: 0879936495; http://www.amazon.com/exec/obidos/ASIN/0879936495/icongroupinterna

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Tachycardia by J. Hambidge; ISBN: 0702124974; http://www.amazon.com/exec/obidos/ASIN/0702124974/icongroupinterna

•

Tachycardias (Developments in Cardiovascular Medicine, 28) by Borys Surawicz; ISBN: 0898385881; http://www.amazon.com/exec/obidos/ASIN/0898385881/icongroupinterna

•

Tachycardias: Mechanisms and Management (The Bakken Research Center, Vol. 6) by Mark E. Josephson, Hein J. J. Wellens (Editor); ISBN: 0879935499; http://www.amazon.com/exec/obidos/ASIN/0879935499/icongroupinterna

•

Tachycardias: Mechanisms, Diagnosis, Treatment by Mark E. Josephson (Editor), Hein J. J. Wellens; ISBN: 081210899X; http://www.amazon.com/exec/obidos/ASIN/081210899X/icongroupinterna

•

Ventricular Tachycardia: Mechanisms and Management by Mark E. Josephson (Editor); ISBN: 0879931817; http://www.amazon.com/exec/obidos/ASIN/0879931817/icongroupinterna

•

Ventricular Tachycardias from Mechanism to Therapy (Developments in Cardiovascular Medicine) by Etienne Aliot, Ralph Lazzara (Editor); ISBN: 0898388813; http://www.amazon.com/exec/obidos/ASIN/0898388813/icongroupinterna

Chapters on Tachycardia In order to find chapters that specifically relate to tachycardia, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and tachycardia using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “tachycardia” (or synonyms) into the “For these words:” box.

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CHAPTER 7. PERIODICALS AND NEWS ON TACHYCARDIA Overview In this chapter, we suggest a number of news sources and present various periodicals that cover tachycardia.

News Services and Press Releases One of the simplest ways of tracking press releases on tachycardia is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “tachycardia” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to tachycardia. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “tachycardia” (or synonyms). The following was recently listed in this archive for tachycardia: •

Glucose-insulin infusion helpful in experimental fetal tachycardia Source: Reuters Medical News Date: February 19, 2004

•

Epicardial radiofrequency ablation helpful in refractory tachycardia Source: Reuters Medical News Date: June 26, 2003

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•

Cardiac implant might control malignant ventricular tachycardia Source: Reuters Medical News Date: January 13, 2003

•

Radiofrequency ablation of post-MI ventricular tachycardia often successful Source: Reuters Medical News Date: November 11, 2002

•

Beta-blockers improve survival in CHD patients with unsustained tachycardia Source: Reuters Medical News Date: October 28, 2002

•

Transmyocardial laser revascularization increases risk of ventricular tachycardia Source: Reuters Medical News Date: July 23, 2002

•

Primary sinus node defect present in subset of postural tachycardia cases Source: Reuters Medical News Date: March 27, 2002

•

Diltiazem safely curbs tachycardia in the critically ill Source: Reuters Industry Breifing Date: November 20, 2001

•

Amiodarone appears safe and effective for infant tachycardia Source: Reuters Medical News Date: January 19, 2001

•

Investigational agent shows promise in treatment of supraventricular tachycardia Source: Reuters Industry Breifing Date: November 23, 2000

•

Tachycardia-related cardiomyopathy common in patients with atrial fibrillation Source: Reuters Medical News Date: August 17, 2000

•

FDA clears Biosense Webster's Navi-Star device for treatment of tachycardia Source: Reuters Industry Breifing Date: July 12, 2000

•

Inducible ventricular tachycardia adds to mortality risk Source: Reuters Medical News Date: June 30, 2000

•

ECG artifact may be misdiagnosed as ventricular tachycardia Source: Reuters Medical News Date: October 22, 1999

•

Beta-blockers not indicated for subset of patients with v fib or symptomatic ventricular tachycardia Source: Reuters Medical News Date: August 02, 1999 The NIH

Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html.

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MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “tachycardia” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “tachycardia” (or synonyms). If you know the name of a company that is relevant to tachycardia, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “tachycardia” (or synonyms).

Academic Periodicals covering Tachycardia Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to tachycardia. In addition to these sources, you can search for articles covering tachycardia that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.”

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If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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CHAPTER 8. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for tachycardia. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP).

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Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/.

PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee.

Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to tachycardia by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on “Orphan Drug Designation Database.” On this page (http://www.rarediseases.org/search/noddsearch.html), type “tachycardia” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for

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marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for tachycardia: •

Amiodarone (trade name: Amio-Aqueous) http://www.rarediseases.org/nord/search/nodd_full?code=543

•

Amiodarone HC1 (trade name: Cordarone) http://www.rarediseases.org/nord/search/nodd_full?code=544

If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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APPENDICES

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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute10: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

•

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

•

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

•

National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

•

National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

•

National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

•

National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

10

These publications are typically written by one or more of the various NIH Institutes.

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National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

•

National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

•

National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

•

National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

•

National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

•

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

•

National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

•

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

•

Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.11 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:12 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

•

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

•

NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

•

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

•

Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

•

Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

•

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

•

Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

•

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

•

MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

11

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 12 See http://www.nlm.nih.gov/databases/databases.html.

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•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html

The NLM Gateway13 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “tachycardia” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 44700 217 190 40 1699 46846

HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.17 Simply search by “tachycardia” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

13

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

14

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 15 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 16 17

The HSTAT URL is http://hstat.nlm.nih.gov/.

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.

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Coffee Break: Tutorials for Biologists18 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.19 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.20 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

The Genome Project and Tachycardia In the following section, we will discuss databases and references which relate to the Genome Project and tachycardia. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).21 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. 18 Adapted 19

from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 20 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process. 21 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.

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To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “tachycardia” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for tachycardia: •

Cardiomyopathy, Dilated, with Ventricular Tachycardia Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=608569

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Tachycardia, Hypertension, Microphthalmos, and Hyperglycinuria Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=272550

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Ventricular Tachycardia, Catecholaminergic Polymorphic Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=604772

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Ventricular Tachycardia, Familial Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=192605 Genes and Disease (NCBI - Map)

The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •

Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html

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Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html

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Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html

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Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html

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Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html

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Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html

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Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez

Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •

3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

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Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books

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Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome

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NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/

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Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide

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OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM

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PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset

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ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

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Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein

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PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

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Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure

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Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy

To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “tachycardia” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database22 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database23 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “tachycardia” (or synonyms) into the search box, and

22

Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 23 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.

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review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on tachycardia can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to tachycardia. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to tachycardia. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “tachycardia”:

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Arrhythmia http://www.nlm.nih.gov/medlineplus/arrhythmia.html Congenital Heart Disease http://www.nlm.nih.gov/medlineplus/congenitalheartdisease.html Heart Attack http://www.nlm.nih.gov/medlineplus/heartattack.html Heart Failure http://www.nlm.nih.gov/medlineplus/heartfailure.html Infertility http://www.nlm.nih.gov/medlineplus/infertility.html Pacemakers and Implantable Defibrillators http://www.nlm.nih.gov/medlineplus/pacemakersandimplantabledefibrillators.ht l Parkinson's Disease http://www.nlm.nih.gov/medlineplus/parkinsonsdisease.html

Within the health topic page dedicated to tachycardia, the following was listed: •

General/Overviews Arrhythmias http://www.nlm.nih.gov/medlineplus/tutorials/arrhythmiasloader.html Cardiac Arrhythmias Source: American College of Cardiology http://www.acc.org/media/patient/chd/cardiac%255Farrhythmias.htm Sudden Cardiac Death Source: North American Society of Pacing and Electrophysiology http://www.naspepatients.org/patients/heart_disorders/cardiac_arrest/index.html What Are Arrhythmias? Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=560

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Diagnosis/Symptoms Diagnosing Arrhythmias Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3 Echocardiogram Source: National Institutes of Health, Clinical Center http://www.cc.nih.gov/ccc/patient_education/procdiag/echocardiogram.pdf Electrophysiology Study (EPS) Source: North American Society of Pacing and Electrophysiology http://www.naspepatients.org/patients/heart_tests/electrophysiology_study.html

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Fainting (Syncope) Source: North American Society of Pacing and Electrophysiology http://www.naspe-patients.org/patients/signs_symptoms/fainting/index.html Other Symptoms of Heart Rhythm Disorders Source: North American Society of Pacing and Electrophysiology http://www.naspe-patients.org/patients/signs_symptoms/other.html Rapid Heartbeat (Tachycardia and Fibrillation) Source: North American Society of Pacing and Electrophysiology http://www.naspe-patients.org/patients/signs_symptoms/too_fast.html Slow Heartbeat (Bradycardia) Source: North American Society of Pacing and Electrophysiology http://www.naspe-patients.org/patients/signs_symptoms/too_slow.html Transesophageal Echocardiogram (TEE) Source: National Institutes of Health, Clinical Center http://www.cc.nih.gov/ccc/patient_education/procdiag/tee.pdf •

Treatment Arrthythmia Medications Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=18 Cardiac Ablation Source: North American Society of Pacing and Electrophysiology http://www.naspe-patients.org/patients/treatments/cardiac_ablation.html Cardiac Ablation Catheter Source: Food and Drug Administration http://www.fda.gov/hearthealth/treatments/medicaldevices/cardiacablationcath eter.html Cardioversion http://circ.ahajournals.org/cgi/reprint/106/22/e176.pdf Catheter Ablation of Arrhythmias http://circ.ahajournals.org/cgi/reprint/106/25/e203.pdf Defibrillation Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=30 Implantable Cardioverter Defibrillators (ICDs) Source: North American Society of Pacing and Electrophysiology http://www.naspepatients.org/patients/treatments/cardiac_defibrillators/index.html Management of Newly Detected Atrial Fibrillation: Recommendations from the American College of Physicians and the American Academy of Family Physicians Source: American College of Physicians http://www.annals.org/cgi/content/full/139/12/I-32

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Nutrition Caffeine, Diet and Heart Arrhythmias Source: North American Society of Pacing and Electrophysiology http://www.naspe-patients.org/patients/substances/diet.html New Guidelines Focus on Fish, Fish Oil, Omega-3 Fatty Acids Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3006624

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Specific Conditions/Aspects Arrhythmias Originating in the Atria Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=10 Arrhythmias Originating in the Ventricles Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=11 Atrial Fibrillation http://www.nlm.nih.gov/medlineplus/tutorials/atrialfibrillationloader.html Atrial Fibrillation Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=DS00291 Bundle Branch Block Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=990 Heart Block Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=992 JAMA Patient Page: Atrial Fibrillation Source: American Medical Association http://www.medem.com/search/article_display.cfm?path=%5C%5CTANQUERA Y%5CM_ContentItem&mstr=/M_ContentItem/ZZZIX1IGUJD.html&soc=JAMA/A rchives&srch_typ=NAV_SERCH Long QT Syndrome Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=DS00434 Long Q-T Syndrome Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=993 Postural Tachycardia Syndrome Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/health_and_medical/disorders/postural_tachycardia_s yndrome.htm Sick Sinus Syndrome http://circ.ahajournals.org/cgi/reprint/108/20/e143.pdf

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Sinus Dysrhythmia Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=AN00787 Substances That Can Cause Heart Rhythm Disorders Source: North American Society of Pacing and Electrophysiology http://www.naspe-patients.org/patients/substances/index.html Sudden Cardiac Death Source: Congenital Heart Information Network http://www.tchin.org/resource_room/c_art_21_.htm Wolff-Parkinson-White Syndrome Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=4785 •

Children Checklist for Parents of Children with Arrhythmias Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=20 Children and Arrhythmia Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=2 Diagnosing Arrhythmias in Children Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=4 Treating Arrhythmias in Children Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=26 Types of Arrhythmia in Children Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=7

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From the National Institutes of Health Facts about Arrhythmias/Rhythm Disorders Source: National Heart, Lung, and Blood Institute http://www.nhlbi.nih.gov/health/public/heart/other/arrhyth.htm

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Latest News Breathing and Heart Problem Often Seen Together Source: 04/09/2004, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_17062 .html New Drug Approach May Fight Lethal Heart Rhythm Source: 04/08/2004, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_17051 .html

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Surgery Cuts Cardiac Arrests among Those with Rare Heart Disorder Source: 03/29/2004, American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3020167 •

Organizations American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=1200000 National Heart, Lung, and Blood Institute http://www.nhlbi.nih.gov/ North American Society of Pacing and Electrophysiology http://www.naspe.org/

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Prevention/Screening Am I at Risk? Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=562 Risk Factors & Prevention Source: North American Society of Pacing and Electrophysiology http://www.naspe-patients.org/patients/risk_factors/index.html

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Research Atrial Fibrillation Hospitalizations Triple Since 1985, Will Continue Climb Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3014151 Blacks Less Likely to Benefit from High-Tech Treatments for Rapid Heartbeat Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3013010 Cardiac Imaging Can Be 'Gatekeeper' for Implantable Heart-Shocker Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3015775 Fish Oils in Heart Cells Can Block Dangerous Heart Rhythms Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3012101 Outcomes of Patients with Lone Atrial Flutter Source: American College of Physicians http://www.annals.org/cgi/content/full/140/4/I-55 Radiofrequency Treatment of Abnormal Heart Rhythm Can Damage the Vessels That Return Blood from the Lungs to the Heart Source: American College of Physicians http://www.annals.org/cgi/content/full/138/8/I-41

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system

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(mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “tachycardia” (or synonyms). The following was recently posted: •

1999 update: ACC/AHA guidelines for the management of patients with acute myocardial infarction. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infar Source: American College of Cardiology Foundation - Medical Specialty Society; 1996 November 1 (revised 1999 Sep); 22 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2006&nbr=1232&a mp;string=tachycardia

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AACE/AAES medical/surgical guidelines for clinical practice: management of thyroid carcinoma Source: American Association of Clinical Endocrinologists - Medical Specialty Society; 1997 (updated 2001 May-Jun); 19 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2848&nbr=2074&a mp;string=rapid+AND+heart+AND+rate

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ACC/AHA 2002 guideline update for exercise testing. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Exercise Testing) Source: American College of Cardiology Foundation - Medical Specialty Society; 1997 July (revised 2002 Sep); 59 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3427&nbr=2653&a mp;string=tachycardia

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ACC/AHA 2002 guideline update for the management of patients with chronic stable angina: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1999 Guidelines for the Managemen Source: American College of Cardiology Foundation - Medical Specialty Society; 1999 June (revised 2002); 127 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3588&nbr=2814&a mp;string=tachycardia

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ACC/AHA 2002 guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Source: American College of Cardiology Foundation - Medical Specialty Society; 2000 (revised online 2002 Mar); 95 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3190&nbr=2416&a mp;string=tachycardia

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ACC/AHA guideline update on perioperative cardiovascular evaluation for noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1996 Guidelines on Perioperati Source: American College of Cardiology Foundation - Medical Specialty Society; 1996 March 15 (revised 2002); 58 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3149&nbr=2375&a mp;string=tachycardia

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ACC/AHA guidelines for coronary artery bypass graft surgery: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1991 Guidelines for Coronary Artery Bypass Graft Surgery) Source: American College of Cardiology Foundation - Medical Specialty Society; 1999 October; 80 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2121&nbr=1347&a mp;string=tachycardia

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ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evalua Source: American College of Cardiology Foundation - Medical Specialty Society; 1995 November 1 (revised 2001 Dec); 56 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3114&nbr=2340&a mp;string=tachycardia

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ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guide Source: American College of Cardiology Foundation - Medical Specialty Society; 2001 October; 70 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2968&nbr=2194&a mp;string=tachycardia

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ACC/AHA/NASPE 2002 guideline update for implantation of cardiac pacemakers and antiarrhythmia devices: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines Source: American College of Cardiology Foundation - Medical Specialty Society; 1998 April (revised 2002 Sep); 48 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3439&nbr=2665&a mp;string=tachycardia

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ACR Appropriateness Criteria™ for acute pancreatitis Source: American College of Radiology - Medical Specialty Society; 1998 (revised 2001); 5 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3257&nbr=2483&a mp;string=tachycardia

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ACR Appropriateness Criteriatm for growth disturbances: risk of intrauterine growth restriction Source: American College of Radiology - Medical Specialty Society; 1996 (revised 2001); 10 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3253&nbr=2479&a mp;string=rapid+AND+heart+AND+rate

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ACR Appropriateness Criteriatm for thrombolysis for lower extremity arterial and graft occlusions Source: American College of Radiology - Medical Specialty Society; 1996 (revised 1999); 14 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2499&nbr=1725&a mp;string=bounding+AND+pulse

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Acute management of autonomic dysreflexia: individuals with spinal cord injury presenting to health-care facilities Source: Consortium for Spinal Cord Medicine - Private Nonprofit Organization; 1997 February (updated 2001 Jul); 29 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2964&nbr=2190&a mp;string=tachycardia

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Acute pain management Source: University of Iowa Gerontological Nursing Interventions Research Center, Research Dissemination Core - Academic Institution; 1997 (revised 1999 April 6); 38 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1888&nbr=1114&a mp;string=rapid+AND+heart+AND+rate

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Allergic rhinitis and its impact on asthma Source: Allergic Rhinitis and its Impact on Asthma Workshop Group - Independent Expert Panel; 2001 November; 188 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3421&nbr=2647&a mp;string=tachycardia

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American Gastroenterological Association medical position statement on obesity Source: American Gastroenterological Association - Medical Specialty Society; 2002 September; 3 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3490&nbr=2716&a mp;string=tachycardia

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Angina pectoris and coronary artery disease (CAD) Source: Finnish Medical Society Duodecim - Professional Association; 2001 April 30 (revised 2003 October 5); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=4372&nbr=3294&a mp;string=rapid+AND+heart+AND+rate

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Antithrombotic therapy in atrial fibrillation. In: Sixth ACCP Consensus Conference on Antithrombotic Therapy Source: American College of Chest Physicians - Medical Specialty Society; 2001 January; 13 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2726&nbr=1952&a mp;string=tachycardia

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Antithrombotic therapy. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 1999 March; 70 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2907&nbr=2133&a mp;string=rapid+AND+heart+AND+rate

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Apnea of prematurity Source: National Association of Neonatal Nurses - Professional Association; 1999; 22 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2147&nbr=1373&a mp;string=tachycardia

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ASHP therapeutic guidelines on the pharmacologic management of nausea and vomiting in adult and pediatric patients receiving chemotherapy or radiation therapy or undergoing surgery Source: American Society of Health-System Pharmacists - Professional Association; 1999; 36 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1875&nbr=1101&a mp;string=tachycardia

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Assessment and management of acute pain Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 2000 October (revised 2002 Oct); 74 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3500&nbr=2726&a mp;string=rapid+AND+heart+AND+rate

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Assessment and management of pain Source: Registered Nurses Association of Ontario - Professional Association; 2002 November; 142 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3720&nbr=2946&a mp;string=tachycardia

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Atrial fibrillation: drug treatment and electric cardioversion Source: Finnish Medical Society Duodecim - Professional Association; 2001 April 30 (revised 2002 March 4); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3377&nbr=2603&a mp;string=tachycardia

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Chemotherapy and biotherapy: guidelines and recommendations for practice Source: Oncology Nursing Society - Professional Association; 2001; 226 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3209&nbr=2435&a mp;string=tachycardia

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Clinical practice guideline for the management of postoperative pain Source: Department of Defense - Federal Government Agency [U.S.]; 2001 July (revised 2002 May); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3284&nbr=2510&a mp;string=tachycardia

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Clinical practice guideline for the management of rheumatoid arthritis Source: Advanced Research Techniques in the Health Services - Private For Profit Research Organization; 2001; 170 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3683&nbr=2909&a mp;string=rapid+AND+heart+AND+rate

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Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult Source: American College of Critical Care Medicine - Professional Association; 1995 (revised 2002); 23 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3171&nbr=2397&a mp;string=rapid+AND+heart+AND+rate

•

Clinical practice parameters for hemodynamic support of pediatric and neonatal patients in septic shock Source: American College of Critical Care Medicine - Professional Association; 2002 June; 14 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3433&nbr=2659&a mp;string=tachycardia

•

Dehydration and fluid maintenance Source: American Medical Directors Association - Professional Association; 2001; 28 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3305&nbr=2531&a mp;string=rapid+AND+heart+AND+rate

•

Delirium: strategies for assessing and treating Source: The John A. Hartford Foundation Institute for Geriatric Nursing - Academic Institution; 2003; 25 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3509&nbr=2735&a mp;string=tachycardia

•

Diagnosis and management of asthma Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1994 August (revised 2003 May); 49 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3874&nbr=3083&a mp;string=tachycardia

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Diagnosis and management of hypertension in the primary care setting Source: Department of Defense - Federal Government Agency [U.S.]; 1999 May; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=2579&nbr=1805&a mp;string=tachycardia

•

Diagnosis of chest pain Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1995 July (revised 2002 Oct); 50 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3674&nbr=2900&a mp;string=tachycardia

•

Epidemic/epizootic West Nile virus in the United States: guidelines for surveillance, prevention, and control Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 2001 April (revised 2003); 75 pages http://www.guideline.gov/summary/summary.aspx?doc_id=4129&nbr=3165&a mp;string=rapid+AND+heart+AND+rate

•

Evidence based clinical practice guideline for managing an acute exacerbation of asthma Source: Cincinnati Children's Hospital Medical Center - Hospital/Medical Center; 1998 July 20 (revised 2002 September 3); 21 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3444&nbr=2670&a mp;string=rapid+AND+heart+AND+rate

•

Evidence-based clinical practice guideline. Nursing care of the woman receiving regional analgesia/anesthesia in labor Source: Association of Women's Health, Obstetric, and Neonatal Nurses - Professional Association; 2001 January; 36 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2928&nbr=2154&a mp;string=tachycardia

•

Evidence-based guidelines for weaning and discontinuation of ventilatory support Source: American Association for Respiratory Care - Professional Association; 2001 December; 21 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3214&nbr=2440&a mp;string=rapid+AND+heart+AND+rate

226

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Exercise prescription for older adults with osteoarthritis pain: consensus practice recommendations Source: American Geriatrics Society - Medical Specialty Society; 2001 June; 16 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3188&nbr=2414&a mp;string=rapid+AND+heart+AND+rate

•

Exercise testing for evaluation of hypoxemia and/or desaturation: 2001 revision and update. Source: American Association for Respiratory Care - Professional Association; 2001 May; 9 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2844&nbr=2070&a mp;string=tachycardia

•

Global initiative for asthma. Global strategy for asthma management and prevention Source: National Heart, Lung, and Blood Institute (U.S.) - Federal Government Agency [U.S.]; 1995 January (revised 2002); 176 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3203&nbr=2429&a mp;string=tachycardia

•

Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease Source: National Heart, Lung, and Blood Institute (U.S.) - Federal Government Agency [U.S.]; 2001; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=2779&nbr=2005&a mp;string=tachycardia

•

Guidelines for Alzheimer's disease management. Source: Alzheimer's Association of Los Angeles, Riverside and San Bernardino Counties - Private Nonprofit Organization; 1999 January 8 (revised 2002 Jan 1); 52 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3157&nbr=2383&a mp;string=tachycardia

•

Guidelines for detection of thyroid dysfunction Source: American Thyroid Association - Professional Association; 2000 June 12; 3 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2361&nbr=1587&a mp;string=tachycardia

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Guidelines for smoking cessation: revised 2002 Source: New Zealand Guidelines Group - Private Nonprofit Organization; 1999 July (revised 2002 May); 33 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3307&nbr=2533&a mp;string=tachycardia

•

Guidelines for the diagnosis and treatment of chronic heart failure Source: European Society of Cardiology - Medical Specialty Society; 2001 September; 34 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2976&nbr=2202&a mp;string=tachycardia

•

Guidelines for the interpretation of the neonatal electrocardiogram Source: European Society of Cardiology - Medical Specialty Society; 2002 September; 16 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3425&nbr=2651&a mp;string=tachycardia

•

Guidelines for the management of leg ulcers in Ireland Source: Smith and Nephew, Ltd. - Private For Profit Organization; 2002; 44 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3616&nbr=2842&a mp;string=rapid+AND+heart+AND+rate

•

Guidelines for the prevention of intravascular catheter-related infections Source: American Academy of Pediatrics - Medical Specialty Society; 1996 (revised 2002 August 9); 36 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3387&nbr=2613&a mp;string=rapid+AND+heart+AND+rate

•

Guidelines on management (diagnosis and treatment) of syncope Source: European Society of Cardiology - Medical Specialty Society; 2001 August; 51 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2974&nbr=2200&a mp;string=tachycardia

•

Heart failure Source: American Medical Directors Association - Professional Association; 1996 (revised 2002); 18 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3303&nbr=2529&a mp;string=tachycardia

228

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Heart Failure Society of America guidelines for management of patients with heart failure caused by left ventricular systolic dysfunction: pharmacological approaches Source: Heart Failure Society of America, Inc - Disease Specific Society; 1999 December; 36 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2736&nbr=1962&a mp;string=tachycardia

•

Identifying and treating eating disorders Source: American Academy of Pediatrics - Medical Specialty Society; 2003 January; 8 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3589&nbr=2815&a mp;string=rapid+AND+heart+AND+rate

•

Infant and family-centered developmental care Source: National Association of Neonatal Nurses - Professional Association; 1993 (revised 2000); 20 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2193&nbr=1419&a mp;string=tachycardia

•

In-hospital transport of the mechanically ventilated patient: 2002 revision and update Source: American Association for Respiratory Care - Professional Association; 1993 December (revised 2002 Jun); 3 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3247&nbr=2473&a mp;string=tachycardia

•

Intrapartum fetal heart rate management Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1994 September (revised 2003 Oct); 27 pages http://www.guideline.gov/summary/summary.aspx?doc_id=4406&nbr=3320&a mp;string=tachycardia

•

Intravenous immunoglobulin preparations Source: University HealthSystem Consortium - Private Nonprofit Organization; 1999 March; 216 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1976&nbr=1202&a mp;string=rapid+AND+heart+AND+rate

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229

Laboratory support for the diagnosis and monitoring of thyroid disease Source: National Academy of Clinical Biochemistry - Professional Association; 2002; 125 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3522&nbr=2748&a mp;string=rapid+AND+heart+AND+rate

•

Major depression, panic disorder and generalized anxiety disorder in adults in primary care Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1996 January (revised 2002 May); 55 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3350&nbr=2576&a mp;string=tachycardia

•

Management of acute coronary syndromes in patients presenting without persistent ST- segment elevation Source: European Society of Cardiology - Medical Specialty Society; 2000 September (revised 2002 Dec); 32 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3518&nbr=2744&a mp;string=tachycardia

•

Management of acute myocardial infarction in patients presenting with ST-segment elevation Source: European Society of Cardiology - Medical Specialty Society; 1996 (revised 2003); 39 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3590&nbr=2816&a mp;string=tachycardia

•

Management of chronic kidney disease and pre-ESRD in the primary care setting Source: Department of Defense - Federal Government Agency [U.S.]; 2000 November; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3099&nbr=2325&a mp;string=rapid+AND+heart+AND+rate

•

Management of diabetes. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 2001 November; 50 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3078&nbr=2304&a mp;string=rapid+AND+heart+AND+rate

230

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Management of preterm labour Source: Chapter of Obstetricians and Gynaecologists, Academy of Medicine (Singapore) - Medical Specialty Society; 2001 May; 28 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2889&nbr=2115&a mp;string=tachycardia

•

Management of type 2 diabetes mellitus Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1996 March (revised 2002 Sep); 77 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3499&nbr=2725&a mp;string=rapid+AND+heart+AND+rate

•

Management of ulcerative colitis Source: Society for Surgery of the Alimentary Tract, Inc - Medical Specialty Society; 2000 (revised 2001); 4 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2967&nbr=2193&a mp;string=tachycardia

•

Myocardial infarction Source: Finnish Medical Society Duodecim - Professional Association; 2001 April 30 (revised 2003 July 11); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=4373&nbr=3295&a mp;string=tachycardia

•

National High Blood Pressure Education Program: Working Group report on high blood pressure in pregnancy Source: National Heart, Lung, and Blood Institute (U.S.) - Federal Government Agency [U.S.]; 1990 (revised 2000 Jul); 39 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1478&nbr=704&am p;string=rapid+AND+heart+AND+rate

•

NKF-K/DOQI clinical practice guidelines for peritoneal dialysis adequacy: update 2000 Source: National Kidney Foundation - Disease Specific Society; 1997 (updated 2000); 72 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2782&nbr=2008&a mp;string=rapid+AND+heart+AND+rate

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NKF-K/DOQI clinical practice guidelines for vascular access: update 2000 Source: National Kidney Foundation - Disease Specific Society; 1997 (updated 2000); 45 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2783&nbr=2009&a mp;string=rapid+AND+heart+AND+rate

•

Physical activity in the prevention, treatment and rehabilitation of diseases Source: Finnish Medical Society Duodecim - Professional Association; 2002 May 7; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3398&nbr=2624&a mp;string=rapid+AND+heart+AND+rate

•

Physical activity/exercise and diabetes Source: American College of Sports Medicine - Medical Specialty Society; 1990 February (revised 1999; republished 2004 Jan); 5 pages http://www.guideline.gov/summary/summary.aspx?doc_id=4683&nbr=3417&a mp;string=tachycardia

•

Practice guideline for evaluation of fever and infection in long-term care facilities Source: Infectious Diseases Society of America - Medical Specialty Society; 2000 September; 14 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2664&nbr=1890&a mp;string=rapid+AND+heart+AND+rate

•

Practice guideline for the treatment of patients with bipolar disorder (revision) Source: American Psychiatric Association - Medical Specialty Society; 1994 December (revised 2002 Apr); 50 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3302&nbr=2528&a mp;string=tachycardia

•

Practice guideline for the treatment of patients with borderline personality disorder Source: American Psychiatric Association - Medical Specialty Society; 2001 October; 52 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2972&nbr=2198&a mp;string=tachycardia

•

Practice guideline for the treatment of patients with delirium Source: American Psychiatric Association - Medical Specialty Society; 1999 May; 41 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2180&nbr=1406&a mp;string=tachycardia

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Practice guidelines for obstetrical anesthesia Source: American Society of Anesthesiologists - Medical Specialty Society; 1999; 11 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1853&nbr=1079&a mp;string=rapid+AND+heart+AND+rate

•

Practice guidelines for the management of infectious diarrhea Source: Infectious Diseases Society of America - Medical Specialty Society; 2001 February; 21 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2791&nbr=2017&a mp;string=tachycardia

•

Practice parameters for the treatment of narcolepsy: an update for 2000. Source: American Academy of Sleep Medicine - Professional Association; 1994 (updated 2001 Jun); 16 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2933&nbr=2159&a mp;string=tachycardia

•

Prevention of thromboembolism in spinal cord injury Source: Consortium for Spinal Cord Medicine - Private Nonprofit Organization; 1997 February (updated 1999 Sep); 29 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2965&nbr=2191&a mp;string=tachycardia

•

Procedure guideline for gastrointestinal bleeding and Meckel's diverticulum scintigraphy Source: Society of Nuclear Medicine, Inc - Medical Specialty Society; 1999 July; 31 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1747&nbr=973&am p;string=tachycardia

•

Procedure guideline for gated equilibrium radionuclide ventriculography Source: Society of Nuclear Medicine, Inc - Medical Specialty Society; 1999 February; 20 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1361&nbr=619&am p;string=tachycardia

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Rhinitis Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1998 August (revised 2003 May); 34 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3875&nbr=3084&a mp;string=tachycardia

•

SAGES guidelines for laparoscopic surgery during pregnancy Source: Society of American Gastrointestinal Endoscopic Surgeons - Medical Specialty Society; 1996 February (revised 2000 Oct); 4 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3146&nbr=2372&a mp;string=tachycardia

•

Schizophrenia Source: Singapore Ministry of Health - National Government Agency [Non-U.S.]; 2003 February; 40 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3750&nbr=2976&a mp;string=tachycardia

•

Specialty referral guidelines for cardiovascular evaluation and management Source: American Healthways, Inc - Public For Profit Organization; 2002; 26 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3168&nbr=2394&a mp;string=tachycardia

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Specialty referral guidelines for people with diabetes Source: American Healthways, Inc - Public For Profit Organization; 1998 (revised 1999); 22 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2005&nbr=1231&a mp;string=tachycardia

•

Task Force on Sudden Cardiac Death of the European Society of Cardiology Source: European Society of Cardiology - Medical Specialty Society; 2001 August; 77 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2977&nbr=2203&a mp;string=tachycardia

•

Task force on the management of chest pain Source: European Society of Cardiology - Medical Specialty Society; 2002 August; 24 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3426&nbr=2652&a mp;string=tachycardia

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The diagnosis and management of urticaria: a practice parameter part I: acute urticaria/angioedema part II: chronic urticaria/angioedema Source: American Academy of Allergy, Asthma and Immunology - Medical Specialty Society; 2000 December; 24 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3622&nbr=2848&a mp;string=rapid+AND+heart+AND+rate

•

The diagnosis and treatment of adult asthma Source: New Zealand Guidelines Group - Private Nonprofit Organization; 2002 September; 101 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3462&nbr=2688&a mp;string=tachycardia

•

The management of diabetes mellitus in the primary care setting Source: Department of Defense - Federal Government Agency [U.S.]; 1999 December; 147 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2583&nbr=1809&a mp;string=tachycardia

•

The management of priapism Source: American Urological Association, Inc. - Medical Specialty Society; 2003; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3741&nbr=2967&a mp;string=tachycardia

•

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure Source: National Heart, Lung, and Blood Institute (U.S.) - Federal Government Agency [U.S.]; 1997 (revised 2003 May 21); 22 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3744&nbr=2970&a mp;string=rapid+AND+heart+AND+rate

•

The use of electronic fetal monitoring. The cardiotocography in intrapartum fetal surveillance

use

and

interpretation

of

Source: Royal College of Obstetricians and Gynaecologists - Medical Specialty Society; 2001 May; 136 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2952&nbr=2178&a mp;string=rapid+AND+heart+AND+rate

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Treatment of acute myocardial infarction Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1996 May (revised 2002 Nov); 68 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3659&nbr=2885&a mp;string=tachycardia

•

Treatment of hypertension in adults with diabetes Source: American Diabetes Association - Professional Association; 2001 October (republished 2003 Jan); 3 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3573&nbr=2799&a mp;string=tachycardia

•

Tularemia as a biological weapon. Medical and public health management Source: Center for Civilian Biodefense Strategies, School of Medicine, Johns Hopkins University - Academic Institution; 2001 June 6; 11 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2981&nbr=2207&a mp;string=rapid+AND+heart+AND+rate

•

Unstable angina pectoris Source: Finnish Medical Society Duodecim - Professional Association; 2001 April 30 (revised 2002 Apr 8); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3383&nbr=2609&a mp;string=rapid+AND+heart+AND+rate

•

Venous thromboembolism Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1998 June (revised 2003 Apr); 93 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3757&nbr=2983&a mp;string=tachycardia

•

VHA/DOD clinical practice guideline for the management of chronic obstructive pulmonary disease. Source: Department of Defense - Federal Government Agency [U.S.]; 1999 August; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=2584&nbr=1810&a mp;string=tachycardia

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VHA/DOD clinical practice guideline for the management of major depressive disorder in adults Source: Department of Defense - Federal Government Agency [U.S.]; 1997 (updated 2000); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=2585&nbr=1811&a mp;string=tachycardia

•

VHA/DoD clinical practice guideline for the management of substance use disorders Source: Department of Defense - Federal Government Agency [U.S.]; 2001 September; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3169&nbr=2395&a mp;string=tachycardia The NIH Search Utility

The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to tachycardia. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

•

Family Village: http://www.familyvillage.wisc.edu/specific.htm

•

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

•

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

•

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

•

WebMDHealth: http://my.webmd.com/health_topics

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to tachycardia. By consulting all of associations listed in

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this chapter, you will have nearly exhausted all sources for patient associations concerned with tachycardia. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about tachycardia. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “tachycardia” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “tachycardia”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “tachycardia” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “tachycardia” (or a synonym) into the search box, and click “Submit Query.”

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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.24

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

24

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)25: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

•

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

•

California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

•

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

•

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

•

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

•

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

•

California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

•

California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

•

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

•

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

•

California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

•

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

•

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

25

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

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•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

•

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

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Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

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Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

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Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

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Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

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Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

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Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

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Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

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Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

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Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

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National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

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National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

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National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

Finding Medical Libraries

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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

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MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

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Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

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On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

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Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

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Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

•

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

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TACHYCARDIA DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 3-dimensional: 3-D. A graphic display of depth, width, and height. Three-dimensional radiation therapy uses computers to create a 3-dimensional picture of the tumor. This allows doctors to give the highest possible dose of radiation to the tumor, while sparing the normal tissue as much as possible. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Abducens: A striated, extrinsic muscle of the eyeball that originates from the annulus of Zinn. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablate: In surgery, is to remove. [NIH] Ablation: The removal of an organ by surgery. [NIH] Abscess: A localized, circumscribed collection of pus. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acetylcholinesterase: An enzyme that catalyzes the hydrolysis of acetylcholine to choline and acetate. In the CNS, this enzyme plays a role in the function of peripheral neuromuscular junctions. EC 3.1.1.7. [NIH] Acidity: The quality of being acid or sour; containing acid (hydrogen ions). [EU] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acrylonitrile: A highly poisonous compound used widely in the manufacture of plastics, adhesives and synthetic rubber. [NIH] Actin: Essential component of the cell skeleton. [NIH] Actinin: A protein factor that regulates the length of R-actin. It is chemically similar, but immunochemically distinguishable from actin. [NIH] Action Potentials: The electric response of a nerve or muscle to its stimulation. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the

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intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenosine Triphosphate: Adenosine 5'-(tetrahydrogen triphosphate). An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. [NIH] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP and pyrophosphate from ATP. EC 4.6.1.1. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adrenergic Agonists: Drugs that bind to and activate adrenergic receptors. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU]

Dictionary 249

Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]

Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Aggressiveness: The quality of being aggressive (= characterized by aggression; militant; enterprising; spreading with vigour; chemically active; variable and adaptable). [EU] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Agranulocytosis: A decrease in the number of granulocytes (basophils, eosinophils, and neutrophils). [NIH] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Airway Resistance: Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. [NIH] Ajmaline: An alkaloid found in the root of Rauwolfia serpentina, among other plant sources. It is a class Ia antiarrhythmic agent that apparently acts by changing the shape and threshold of cardiac action potentials. [NIH] Albuterol: A racemic mixture with a 1:1 ratio of the r-isomer, levalbuterol, and s-albuterol. It is a short-acting beta 2-adrenergic agonist with its main clinical use in asthma. [NIH] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Alloys: A mixture of metallic elements or compounds with other metallic or metalloid elements in varying proportions. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alternans: Ipsilateral abducens palsy and facial paralysis and contralateral hemiplegia of the limbs, due to a nuclear or infranuclear lesion in the pons. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy,

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magnet therapy, spiritual healing, and meditation. [NIH] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Amebiasis: Infection with any of various amebae. It is an asymptomatic carrier state in most individuals, but diseases ranging from chronic, mild diarrhea to fulminant dysentery may occur. [NIH] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amiodarone: An antianginal and antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting Na,K-activated myocardial adenosine triphosphatase. There is a resulting decrease in heart rate and in vascular resistance. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Amputation: Surgery to remove part or all of a limb or appendage. [NIH] Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [NIH]

Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH]

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Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] Angioedema: A vascular reaction involving the deep dermis or subcutaneous or submucal tissues, representing localized edema caused by dilatation and increased permeability of the capillaries, and characterized by development of giant wheals. [EU] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anomalies: Birth defects; abnormalities. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Antianginal: Counteracting angina or anginal conditions. [EU] Antiarrhythmic: An agent that prevents or alleviates cardiac arrhythmia. [EU] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticholinergic: An agent that blocks the parasympathetic nerves. Called also parasympatholytic. [EU] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidepressant: A drug used to treat depression. [NIH] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]

Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble

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substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antihypertensive: An agent that reduces high blood pressure. [EU] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antimitotic: Inhibiting or preventing mitosis. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antispasmodic: An agent that relieves spasm. [EU] Antitussive: An agent that relieves or prevents cough. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiety Disorders: Disorders in which anxiety (persistent feelings of apprehension, tension, or uneasiness) is the predominant disturbance. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Aortic Valve: The valve between the left ventricle and the ascending aorta which prevents backflow into the left ventricle. [NIH] Apnea: A transient absence of spontaneous respiration. [NIH] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Aponeurosis: Tendinous expansion consisting of a fibrous or membranous sheath which serves as a fascia to enclose or bind a group of muscles. [NIH] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH] Arrhythmogenic: Producing or promoting arrhythmia. [EU] Arrhythmogenic Right Ventricular Dysplasia: A weakening of the right ventricle that results in the back up of blood in the venous system, liver, gastrointestinal tract, and extremities. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteriolar: Pertaining to or resembling arterioles. [EU] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriosus: Circle composed of anastomosing arteries derived from two long posterior

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ciliary and seven anterior ciliary arteries, located in the ciliary body about the root of the iris. [NIH]

Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Articular: Of or pertaining to a joint. [EU] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH] Aspartate: A synthetic amino acid. [NIH] Asphyxia: A pathological condition caused by lack of oxygen, manifested in impending or actual cessation of life. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asymptomatic: Having no signs or symptoms of disease. [NIH] Asynchronous: Pacing mode where only one timing interval exists, that between the stimuli. While the duration of this interval may be varied, it is not modified by any sensed event once set. As no sensing occurs, the upper and lower rate intervals are the same as the pacema. [NIH] Asystole: Cardiac standstill or arrest; absence of a heartbeat; called also Beau's syndrome. [EU]

Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atrial: Pertaining to an atrium. [EU] Atrial Fibrillation: Disorder of cardiac rhythm characterized by rapid, irregular atrial impulses and ineffective atrial contractions. [NIH] Atrial Flutter: Rapid, irregular atrial contractions due to an abnormality of atrial excitation. [NIH]

Atrial Function: The hemodynamic and electrophysiological action of the atria. [NIH] Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Atrioventricular Node: A small nodular mass of specialized muscle fibers located in the interatrial septum near the opening of the coronary sinus. It gives rise to the atrioventricular bundle of the conduction system of the heart. [NIH] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Atropine: A toxic alkaloid, originally from Atropa belladonna, but found in other plants, mainly Solanaceae. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH]

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Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Auditory: Pertaining to the sense of hearing. [EU] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Dysreflexia: That part of the nervous system concerned with the unconscious regulation of the living processes of the body. [NIH] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Autonomic Neuropathy: A disease of the nerves affecting mostly the internal organs such as the bladder muscles, the cardiovascular system, the digestive tract, and the genital organs. These nerves are not under a person's conscious control and function automatically. Also called visceral neuropathy. [NIH] Autosuggestion: Suggestion coming from the subject himself. [NIH] Axillary: Pertaining to the armpit area, including the lymph nodes that are located there. [NIH]

Axillary Vein: The venous trunk of the upper limb; a continuation of the basilar and brachial veins running from the lower border of the teres major muscle to the outer border of the first rib where it becomes the subclavian vein. [NIH] Bacteremia: The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Barium: An element of the alkaline earth group of metals. It has an atomic symbol Ba, atomic number 56, and atomic weight 138. All of its acid-soluble salts are poisonous. [NIH] Baroreflex: A negative feedback system which buffers short-term changes in blood pressure. Increased pressure stretches blood vessels which activates pressoreceptors (baroreceptors) in

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the vessel walls. The net response of the central nervous system is a reduction of central sympathetic outflow. This reduces blood pressure both by decreasing peripheral vascular resistance and by lowering cardiac output. Because the baroreceptors are tonically active, the baroreflex can compensate rapidly for both increases and decreases in blood pressure. [NIH]

Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Belladonna: A species of very poisonous Solanaceous plants yielding atropine (hyoscyamine), scopolamine, and other belladonna alkaloids, used to block the muscarinic autonomic nervous system. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH]

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Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Bipolar Disorder: A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence. [NIH] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Blood Cell Count: A count of the number of leukocytes and erythrocytes per unit volume in a sample of venous blood. A complete blood count (CBC) also includes measurement of the hemoglobin, hematocrit, and erythrocyte indices. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Flow Velocity: A value equal to the total volume flow divided by the cross-sectional area of the vascular bed. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood Volume: Volume of circulating blood. It is the sum of the plasma volume and erythrocyte volume. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Body Fluids: Liquid components of living organisms. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [NIH] Bolus: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus infusion. [NIH]

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Bolus infusion: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachiocephalic Veins: Large veins on either side of the root of the neck formed by the junction of the internal jugular and subclavian veins. They drain blood from the head, neck, and upper extremities, and unite to form the superior vena cava. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradycardia: Excessive slowness in the action of the heart, usually with a heart rate below 60 beats per minute. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bronchoconstriction: Diminution of the caliber of a bronchus physiologically or as a result of pharmacological intervention. [NIH] Bronchodilator: A drug that relaxes the smooth muscles in the constricted airway. [NIH] Bronchopulmonary: Pertaining to the lungs and their air passages; both bronchial and pulmonary. [EU] Bronchus: A large air passage that leads from the trachea (windpipe) to the lung. [NIH] Buffers: A chemical system that functions to control the levels of specific ions in solution. When the level of hydrogen ion in solution is controlled the system is called a pH buffer. [NIH]

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Bullous: Pertaining to or characterized by bullae. [EU] Bundle-Branch Block: A form of heart block in which one ventricle is excited before the other because of absence of conduction in one of the branches of the bundle of His. [NIH] Bupivacaine: A widely used local anesthetic agent. [NIH] Burns: Injuries to tissues caused by contact with heat, steam, chemicals (burns, chemical), electricity (burns, electric), or the like. [NIH] Burns, Electric: Burns produced by contact with electric current or from a sudden discharge of electricity. [NIH] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium channel blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH]

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Cardiac arrest: A sudden stop of heart function. [NIH] Cardiac catheterization: A procedure in which a thin, hollow tube is inserted into a blood vessel. The tube is then advanced through the vessel into the heart, enabling a physician to study the heart and its pumping activity. [NIH] Cardiac Glycosides: Substances obtained from species of Digitalis, Strophanthus, and other plants that contain specific steroid glycosides or their semisynthetic derivatives and used in congestive heart failure. They increase the force of cardiac contraction without significantly affecting other parameters, but are very toxic at larger doses. Their mechanism of action usually involves inhibition of the Na(+)-K(+)-exchanging ATPase and they are often used in cell biological studies for that purpose. [NIH] Cardiac Output: The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). [NIH] Cardiological: Relating to the study of the heart. [EU] Cardiology: The study of the heart, its physiology, and its functions. [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiomyopathy, Hypertrophic: A myocardial disease characterized by hypertrophy, involving mainly the interventricular septum, interfering with left ventricular emptying. [NIH]

Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardioselective: Having greater activity on heart tissue than on other tissue. [EU] Cardiotocography: Monitoring of fetal heart frequency before birth in order to assess impending prematurity in relation to the pattern or intensity of antepartum uterine contraction. [NIH] Cardiotonic: 1. Having a tonic effect on the heart. 2. An agent that has a tonic effect on the heart. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular Abnormalities: Congenital structural abnormalities of the cardiovascular system. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Cardiovascular Physiology: Functions and activities of the cardiovascular system as a whole or of any of its parts. [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH] Cardioversion: Electrical reversion of cardiac arrhythmias to normal sinus rhythm, formerly using alternatic current, but now employing direct current. [NIH] Carotid Body: A small cluster of chemoreceptive and supporting cells located near the bifurcation of the internal carotid artery. The carotid body, which is richly supplied with fenestrated capillaries, senses the pH, carbon dioxide, and oxygen concentrations in the blood and plays a crucial role in their homeostatic control. [NIH] Carotid Sinus: The dilated portion of the common carotid artery at its bifurcation into external and internal carotids. It contains baroreceptors which, when stimulated, cause

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slowing of the heart, vasodilatation, and a fall in blood pressure. [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [NIH] Catheter Ablation: Removal of tissue with electrical current delivered via electrodes positioned at the distal end of a catheter. Energy sources are commonly direct current (DCshock) or alternating current at radiofrequencies (usually 750 kHz). The technique is used most often to ablate the AV junction and/or accessory pathways in order to interrupt AV conduction and produce AV block in the treatment of various tachyarrhythmias. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Cefotaxime: Semisynthetic broad-spectrum cephalosporin. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell Fusion: Fusion of somatic cells in vitro or in vivo, which results in somatic cell hybridization. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain

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functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Central Venous Pressure: The blood pressure in the central large veins of the body. It is distinguished from peripheral venous pressure which occurs in an extremity. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellar Diseases: Diseases that affect the structure or function of the cerebellum. Cardinal manifestations of cerebellar dysfunction include dysmetria, gait ataxia, and muscle hypotonia. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrovascular Circulation: The circulation of blood through the vessels of the brain. [NIH] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Cesium: A member of the alkali metals. It has an atomic symbol Cs, atomic number 50, and atomic weight 132.91. Cesium has many industrial applications, including the construction of atomic clocks based on its atomic vibrational frequency. [NIH] Chaos: Complex behavior that seems random but actually has some hidden order. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] CHD: Coronary heart disease. A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Chemoreceptor: A receptor adapted for excitation by chemical substances, e.g., olfactory and gustatory receptors, or a sense organ, as the carotid body or the aortic (supracardial) bodies, which is sensitive to chemical changes in the blood stream, especially reduced oxygen content, and reflexly increases both respiration and blood pressure. [EU] Chemotherapy: Treatment with anticancer drugs. [NIH] Chest Pain: Pressure, burning, or numbness in the chest. [NIH]

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Chest wall: The ribs and muscles, bones, and joints that make up the area of the body between the neck and the abdomen. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic Fatigue Syndrome: Fatigue caused by the combined effects of different types of prolonged fatigue. [NIH] Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Circadian: Repeated more or less daily, i. e. on a 23- to 25-hour cycle. [NIH] Circadian Rhythm: The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs and stimuli, hormone secretion, sleeping, feeding, etc. This rhythm seems to be set by a 'biological clock' which seems to be set by recurring daylight and darkness. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [NIH] Citrus: Any tree or shrub of the Rue family or the fruit of these plants. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH]

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Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Codeine: An opioid analgesic related to morphine but with less potent analgesic properties and mild sedative effects. It also acts centrally to suppress cough. [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Colectomy: An operation to remove the colon. An open colectomy is the removal of the colon through a surgical incision made in the wall of the abdomen. Laparoscopic-assisted colectomy uses a thin, lighted tube attached to a video camera. It allows the surgeon to remove the colon without a large incision. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Colonoscopy: Endoscopic examination, therapy or surgery of the luminal surface of the colon. [NIH] Colostomy: An opening into the colon from the outside of the body. A colostomy provides a new path for waste material to leave the body after part of the colon has been removed. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH]

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Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computer Simulation: Computer-based representation of physical systems and phenomena such as chemical processes. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU]

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Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connexins: A group of homologous proteins which form the intermembrane channels of gap junctions. The connexins are the products of an identified gene family which has both highly conserved and highly divergent regions. The variety contributes to the wide range of functional properties of gap junctions. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contractility: Capacity for becoming short in response to a suitable stimulus. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contralateral: Having to do with the opposite side of the body. [NIH] Contrast medium: A substance that is introduced into or around a structure and, because of the difference in absorption of x-rays by the contrast medium and the surrounding tissues, allows radiographic visualization of the structure. [EU] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Conus: A large, circular, white patch around the optic disk due to the exposing of the sclera as a result of degenerative change or congenital abnormality in the choroid and retina. [NIH] Conventional therapy: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional treatment. [NIH] Conventional treatment: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional therapy. [NIH] Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a

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pathologic involvement of them. [EU] Coronary Arteriosclerosis: Thickening and loss of elasticity of the coronary arteries. [NIH] Coronary Artery Bypass: Surgical therapy of ischemic coronary artery disease achieved by grafting a section of saphenous vein, internal mammary artery, or other substitute between the aorta and the obstructed coronary artery distal to the obstructive lesion. [NIH] Coronary Circulation: The circulation of blood through the coronary vessels of the heart. [NIH]

Coronary Disease: Disorder of cardiac function due to an imbalance between myocardial function and the capacity of the coronary vessels to supply sufficient flow for normal function. It is a form of myocardial ischemia (insufficient blood supply to the heart muscle) caused by a decreased capacity of the coronary vessels. [NIH] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Coronary Vessels: The veins and arteries of the heart. [NIH] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroids: Hormones that have antitumor activity in lymphomas and lymphoid leukemias; in addition, corticosteroids (steroids) may be used for hormone replacement and for the management of some of the complications of cancer and its treatment. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Criterion: A standard by which something may be judged. [EU] Curative: Tending to overcome disease and promote recovery. [EU] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyst: A sac or capsule filled with fluid. [NIH] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which

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contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some nonleukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [NIH] Decompression: Decompression external to the body, most often the slow lessening of external pressure on the whole body (especially in caisson workers, deep sea divers, and persons who ascend to great heights) to prevent decompression sickness. It includes also sudden accidental decompression, but not surgical (local) decompression or decompression applied through body openings. [NIH] Defibrillation: The act to arrest the fibrillation of (heart muscle) by applying electric shock across the chest, thus depolarizing the heart cells and allowing normal rhythm to return. [EU] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydration: The condition that results from excessive loss of body water. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delirium: (DSM III-R) an acute, reversible organic mental disorder characterized by reduced ability to maintain attention to external stimuli and disorganized thinking as manifested by rambling, irrelevant, or incoherent speech; there are also a reduced level of consciousness, sensory misperceptions, disturbance of the sleep-wakefulness cycle and level of psychomotor activity, disorientation to time, place, or person, and memory impairment.

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Delirium may be caused by a large number of conditions resulting in derangement of cerebral metabolism, including systemic infection, poisoning, drug intoxication or withdrawal, seizures or head trauma, and metabolic disturbances such as hypoxia, hypoglycaemia, fluid, electrolyte, or acid-base imbalances, or hepatic or renal failure. Called also acute confusional state and acute brain syndrome. [EU] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] Delusions: A false belief regarding the self or persons or objects outside the self that persists despite the facts, and is not considered tenable by one's associates. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dentition: The teeth in the dental arch; ordinarily used to designate the natural teeth in position in their alveoli. [EU] Depersonalization: Alteration in the perception of the self so that the usual sense of one's own reality is lost, manifested in a sense of unreality or self-estrangement, in changes of body image, or in a feeling that one does not control his own actions and speech; seen in depersonalization disorder, schizophrenic disorders, and schizotypal personality disorder. Some do not draw a distinction between depersonalization and derealization, using depersonalization to include both. [EU] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [NIH] Derealization: Is characterized by the loss of the sense of reality concerning one's surroundings. [NIH] Dermatitis: Any inflammation of the skin. [NIH] Dermatitis Herpetiformis: Rare, chronic, papulo-vesicular disease characterized by an intensely pruritic eruption consisting of various combinations of symmetrical, erythematous, papular, vesicular, or bullous lesions. The disease is strongly associated with the presence of HLA-B8 and HLA-DR3 antigens. A variety of different autoantibodies has been detected in small numbers in patients with dermatitis herpetiformis. [NIH] Dermatosis: Any skin disease, especially one not characterized by inflammation. [EU] Dermis: A layer of vascular connective tissue underneath the epidermis. The surface of the dermis contains sensitive papillae. Embedded in or beneath the dermis are sweat glands, hair follicles, and sebaceous glands. [NIH] Detergents: Purifying or cleansing agents, usually salts of long-chain aliphatic bases or acids, that exert cleansing (oil-dissolving) and antimicrobial effects through a surface action that depends on possessing both hydrophilic and hydrophobic properties. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diabetic Ketoacidosis: Complication of diabetes resulting from severe insulin deficiency coupled with an absolute or relative increase in glucagon concentration. The metabolic acidosis is caused by the breakdown of adipose stores and resulting increased levels of free

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fatty acids. Glucagon accelerates the oxidation of the free fatty acids producing excess ketone bodies (ketosis). [NIH] Diagnostic Errors: Incorrect diagnoses after clinical examination or technical diagnostic procedures. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diaphoresis: Perspiration, especially profuse perspiration. Called also sudoresis. [EU] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] Diastole: Period of relaxation of the heart, especially the ventricles. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Digitalis: A genus of toxic herbaceous Eurasian plants of the Scrophulaceae which yield cardiotonic glycosides. The most useful are Digitalis lanata and D. purpurea. [NIH] Dihydroprogesterone: 20 alpha-Hydroxypregn-4-en-3-one. progesterone derivative with progestational activity. [NIH]

A

naturally

occurring

Dilatation: The act of dilating. [NIH] Dilatation, Pathologic: The condition of an anatomical structure's being dilated beyond normal dimensions. [NIH] Dilated cardiomyopathy: Heart muscle disease that leads to enlargement of the heart's chambers, robbing the heart of its pumping ability. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Diltiazem: A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of the calcium ion in membrane functions. It is also teratogenic. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disopyramide: Alpha-(2-(Bis(l-methylethyl)amino)ethyl)-alpha-phenyl-2-pyridine acetamide. A class I anti-arrhythmic agent (one that interferes directly with the depolarization of the cardiac membrane and thus serves as a membrane-stabilizing agent) with a depressant action on the heart similar to that of guanidine. It also possesses some anticholinergic and local anesthetic properties. [NIH]

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Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Dissection: Cutting up of an organism for study. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions of consciousness. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [EU] Diverticulum: A pathological condition manifested as a pouch or sac opening from a tubular or sacular organ. [NIH] Diving: An activity in which the organism plunges into water. It includes scuba and bell diving. Diving as natural behavior of animals goes here, as well as diving in decompression experiments with humans or animals. [NIH] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Dobutamine: A beta-2 agonist catecholamine that has cardiac stimulant action without evoking vasoconstriction or tachycardia. It is proposed as a cardiotonic after myocardial infarction or open heart surgery. [NIH] Docosahexaenoic Acids: C22-unsaturated fatty acids found predominantly in fish oils. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH]

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Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dysphoric: A feeling of unpleasantness and discomfort. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Dystrophin: A muscle protein localized in surface membranes which is the product of the Duchenne/Becker muscular dystrophy gene. Individuals with Duchenne muscular dystrophy usually lack dystrophin completely while those with Becker muscular dystrophy have dystrophin of an altered size. It shares features with other cytoskeletal proteins such as spectrin and alpha-actinin but the precise function of dystrophin is not clear. One possible role might be to preserve the integrity and alignment of the plasma membrane to the myofibrils during muscle contraction and relaxation. MW 400 kDa. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Eating Disorders: A group of disorders characterized by physiological and psychological disturbances in appetite or food intake. [NIH] Echocardiography: Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. [NIH] Eclampsia: Onset of convulsions or coma in a previously diagnosed pre-eclamptic patient. [NIH]

Ectoderm: The outer of the three germ layers of the embryo. [NIH] Ectopic: Pertaining to or characterized by ectopia. [EU] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efferent: Nerve fibers which conduct impulses from the central nervous system to muscles and glands. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Ejection fraction: A measure of ventricular contractility, equal to normally 65 8 per cent; lower values indicate ventricular dysfunction. [EU] Elastin: The protein that gives flexibility to tissues. [NIH] Elastomers: A generic term for all substances having the properties of natural, reclaimed, vulcanized, or synthetic rubber, in that they stretch under tension, have a high tensile strength, retract rapidly, and recover their original dimensions fully. [NIH]

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Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electric Conductivity: The ability of a substrate to allow the passage of electrons. [NIH] Electric shock: A dangerous patho-physiological effect resulting from an electric current passing through the body of a human or animal. [NIH] Electrocardiogram: Measurement of electrical activity during heartbeats. [NIH] Electrocardiography: Recording of the moment-to-moment electromotive forces of the heart as projected onto various sites on the body's surface, delineated as a scalar function of time. [NIH]

Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electromagnetic Fields: Fields representing the joint interplay of electric and magnetic forces. [NIH] Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Electroporation: A technique in which electric pulses of intensity in kilovolts per centimeter and of microsecond-to-millisecond duration cause a temporary loss of the semipermeability of cell membranes, thus leading to ion leakage, escape of metabolites, and increased uptake by cells of drugs, molecular probes, and DNA. Some applications of electroporation include introduction of plasmids or foreign DNA into living cells for transfection, fusion of cells to prepare hybridomas, and insertion of proteins into cell membranes. [NIH] Emboli: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embolization: The blocking of an artery by a clot or foreign material. Embolization can be done as treatment to block the flow of blood to a tumor. [NIH] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryology: The study of the development of an organism during the embryonic and fetal stages of life. [NIH] Emergency Medical Services: Services specifically designed, staffed, and equipped for the emergency care of patients. [NIH] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Encephalomalacia: Literally, "softening of the brain", but the term is used to include degenerative diseases of the brain generally, due to a variety of causes. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU]

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Endocardium: The innermost layer of the heart, comprised of endothelial cells. [NIH] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endorphins: One of the three major groups of endogenous opioid peptides. They are large peptides derived from the pro-opiomelanocortin precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; opioid peptides is used for the broader group. [NIH] Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Energy balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH] Energy Intake: Total number of calories taken in daily whether ingested or by parenteral routes. [NIH] Enkephalins: One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH]

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Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epizootic: A disease of high morbidity which is only occasionally present in an animal community: it affects a great number of animals in a large area of land at the same time and spreads with great rapidity over a wide territory. [NIH] Erection: The condition of being made rigid and elevated; as erectile tissue when filled with blood. [EU] ERV: The expiratory reserve volume is the largest volume of gas that can be expired from the end-expiratory level. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythema Nodosum: An erythematous eruption commonly associated with drug reactions or infection and characterized by inflammatory nodules that are usually tender, multiple, and bilateral. These nodules are located predominantly on the shins with less common occurrence on the thighs and forearms. They undergo characteristic color changes ending in temporary bruise-like areas. This condition usually subsides in 3-6 weeks without scarring or atrophy. [NIH] Erythrocyte Indices: Quantification of size and cell hemoglobin content or concentration of the erythrocyte, usually derived from erythrocyte count, blood hemoglobin concentration, and hematocrit. Includes the mean cell volume (MCV), mean cell hemoglobin (MCH), and mean cell hemoglobin concentration (MCHC). Use also for cell diameter and thickness. [NIH] Erythrocyte Volume: Volume of circulating erythrocytes. It is usually measured by radioisotope dilution technique. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophageal Varices: Stretched veins in the esophagus that occur when the liver is not working properly. If the veins burst, the bleeding can cause death. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ethanolamine: A viscous, hygroscopic amino alcohol with an ammoniacal odor. It is widely distributed in biological tissue and is a component of lecithin. It is used as a surfactant, fluorimetric reagent, and to remove CO2 and H2S from natural gas and other gases. [NIH]

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Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [NIH] Etoposide: A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Exercise Test: Controlled physical activity, more strenuous than at rest, which is performed in order to allow assessment of physiological functions, particularly cardiovascular and pulmonary, but also aerobic capacity. Maximal (most intense) exercise is usually required but submaximal exercise is also used. The intensity of exercise is often graded, using criteria such as rate of work done, oxygen consumption, and heart rate. Physiological data obtained from an exercise test may be used for diagnosis, prognosis, and evaluation of disease severity, and to evaluate therapy. Data may also be used in prescribing exercise by determining a person's exercise capacity. [NIH] Exercise Tolerance: The exercise capacity of an individual as measured by endurance (maximal exercise duration and/or maximal attained work load) during an exercise test. [NIH]

Exhaustion: The feeling of weariness of mind and body. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exons: Coding regions of messenger RNA included in the genetic transcript which survive the processing of RNA in cell nuclei to become part of a spliced messenger of structural RNA in the cytoplasm. They include joining and diversity exons of immunoglobulin genes. [NIH]

Expiratory: The volume of air which leaves the breathing organs in each expiration. [NIH] Expiratory Reserve Volume: The extra volume of air that can be expired with maximum effort beyond the level reached at the end of a normal, quiet expiration. Common abbreviation is ERV. [NIH] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH]

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Extrapyramidal: Outside of the pyramidal tracts. [EU] Extrasystole: A premature contraction of the heart that is independent of the normal rhythm and arises in response to an impulse in some part of the heart other than the sinoatrial node; called also premature beat. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Exudate: Material, such as fluid, cells, or cellular debris, which has escaped from blood vessels and has been deposited in tissues or on tissue surfaces, usually as a result of inflammation. An exudate, in contrast to a transudate, is characterized by a high content of protein, cells, or solid materials derived from cells. [EU] Facial: Of or pertaining to the face. [EU] Facial Paralysis: Severe or complete loss of facial muscle motor function. This condition may result from central or peripheral lesions. Damage to CNS motor pathways from the cerebral cortex to the facial nuclei in the pons leads to facial weakness that generally spares the forehead muscles. Facial nerve diseases generally results in generalized hemifacial weakness. Neuromuscular junction diseases and muscular diseases may also cause facial paralysis or paresis. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Febrile: Pertaining to or characterized by fever. [EU] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Fenoterol: An adrenergic beta-2 agonist that is used as a bronchodilator and tocolytic. [NIH] Fetal Blood: Blood of the fetus. Exchange of nutrients and waste between the fetal and maternal blood occurs via the placenta. The cord blood is blood contained in the umbilical vessels at the time of delivery. [NIH] Fetal Development: Morphologic and physiologic growth and development of the mammalian embryo or fetus. [NIH] Fetal Heart: The heart of the fetus of any viviparous animal. It refers to the heart in the postembryonic period and is differentiated from the embryonic heart (heart/embryology) only on the basis of time. [NIH] Fetal Monitoring: Physiologic or biochemical monitoring of the fetus. It is usually done during labor and may be performed in conjunction with the monitoring of uterine activity. It may also be performed prenatally as when the mother is undergoing surgery. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrillation: A small, local, involuntary contraction of muscle, invisible under the skin, resulting from spontaneous activation of single muscle cells or muscle fibres. [EU] Fibroma: A benign tumor of fibrous or fully developed connective tissue. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ,

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usually as a consequence of inflammation or other injury. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Fish Oils: Oils high in unsaturated fats extracted from the bodies of fish or fish parts, especially the livers. Those from the liver are usually high in vitamin A. The oils are used as dietary supplements, in soaps and detergents, as protective coatings, and as a base for other food products such as vegetable shortenings. [NIH] Flatus: Gas passed through the rectum. [NIH] Flecainide: A potent anti-arrhythmia agent, effective in a wide range of ventricular and atrial arrhythmias and tachycardias. Paradoxically, however, in myocardial infarct patients with either symptomatic or asymptomatic arrhythmia, flecainide exacerbates the arrhythmia and is not recommended for use in these patients. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Flutter: A rapid vibration or pulsation. [EU] Fold: A plication or doubling of various parts of the body. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Friction: Surface resistance to the relative motion of one body against the rubbing, sliding, rolling, or flowing of another with which it is in contact. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Ganglionic Blockers: Agents having as their major action the interruption of neural transmission at nicotinic receptors on postganglionic autonomic neurons. Because their actions are so broad, including blocking of sympathetic and parasympathetic systems, their therapeutic use has been largely supplanted by more specific drugs. They may still be used in the control of blood pressure in patients with acute dissecting aortic aneurysm and for the induction of hypotension in surgery. [NIH] Gap Junctions: Connections between cells which allow passage of small molecules and

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electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Generator: Any system incorporating a fixed parent radionuclide from which is produced a daughter radionuclide which is to be removed by elution or by any other method and used in a radiopharmaceutical. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]

Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Giant Cells: Multinucleated masses produced by the fusion of many cells; often associated with viral infections. In AIDS, they are induced when the envelope glycoprotein of the HIV virus binds to the CD4 antigen of uninfected neighboring T4 cells. The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus. [NIH] Giardiasis: An infection of the small intestine caused by the flagellated protozoan Giardia lamblia. It is spread via contaminated food and water and by direct person-to-person contact. [NIH] Gland: An organ that produces and releases one or more substances for use in the body.

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Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glucose tolerance: The power of the normal liver to absorb and store large quantities of glucose and the effectiveness of intestinal absorption of glucose. The glucose tolerance test is a metabolic test of carbohydrate tolerance that measures active insulin, a hepatic function based on the ability of the liver to absorb glucose. The test consists of ingesting 100 grams of glucose into a fasting stomach; blood sugar should return to normal in 2 to 21 hours after ingestion. [NIH] Glucose Tolerance Test: Determination of whole blood or plasma sugar in a fasting state before and at prescribed intervals (usually 1/2 hr, 1 hr, 3 hr, 4 hr) after taking a specified amount (usually 100 gm orally) of glucose. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins. [NIH] Glycoside: Any compound that contains a carbohydrate molecule (sugar), particularly any such natural product in plants, convertible, by hydrolytic cleavage, into sugar and a nonsugar component (aglycone), and named specifically for the sugar contained, as glucoside (glucose), pentoside (pentose), fructoside (fructose) etc. [EU] Gonadal: Pertaining to a gonad. [EU] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Groin: The external junctural region between the lower part of the abdomen and the thigh. [NIH]

Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH]

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Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] Haematoma: A localized collection of blood, usually clotted, in an organ, space, or tissue, due to a break in the wall of a blood vessel. [EU] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Hamartoma: A focal malformation resembling a neoplasm, composed of an overgrowth of mature cells and tissues that normally occur in the affected area. [NIH] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Health Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH] Health Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heart Transplantation: The transference of a heart from one human or animal to another. [NIH]

Heartbeat: One complete contraction of the heart. [NIH] Hematocrit: Measurement of the volume of packed red cells in a blood specimen by centrifugation. The procedure is performed using a tube with graduated markings or with automated blood cell counters. It is used as an indicator of erythrocyte status in disease. For example, anemia shows a low hematocrit, polycythemia, high values. [NIH]

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Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemiplegia: Severe or complete loss of motor function on one side of the body. This condition is usually caused by BRAIN DISEASES that are localized to the cerebral hemisphere opposite to the side of weakness. Less frequently, BRAIN STEM lesions; cervical spinal cord diseases; peripheral nervous system diseases; and other conditions may manifest as hemiplegia. The term hemiparesis (see paresis) refers to mild to moderate weakness involving one side of the body. [NIH] Hemodynamics: The movements of the blood and the forces involved in systemic or regional blood circulation. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemolysis: The destruction of erythrocytes by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemorrhoids: Varicosities of the hemorrhoidal venous plexuses. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Hepatic: Refers to the liver. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herpetiformis: Duhring's disease a recurring, inflammatory disease of the skin of unknown etiology characterized by erythematous, papular, pustular, or vesicular lesions which tend to group and are accompanied by itching and burning. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Heterozygote: An individual having different alleles at one or more loci in homologous chromosome segments. [NIH] Hexamethonium: A nicotinic cholinergic antagonist often referred to as the prototypical ganglionic blocker. It is poorly absorbed from the gastrointestinal tract and does not cross the blood-brain barrier. It has been used for a variety of therapeutic purposes including hypertension but, like the other ganglionic blockers, it has been replaced by more specific

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drugs for most purposes, although it is widely used a research tool. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Homozygote: An individual in which both alleles at a given locus are identical. [NIH] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperoxaluria: Excretion of an excessive amount of oxalate in the urine. [NIH] Hyperphagia: Ingestion of a greater than optimal quantity of food. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthyroidism: Excessive functional activity of the thyroid gland. [NIH] Hypertrophic cardiomyopathy: Heart muscle disease that leads to thickening of the heart walls, interfering with the heart's ability to fill with and pump blood. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH]

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Hypesthesia: Absent or reduced sensitivity to cutaneous stimulation. [NIH] Hypocapnia: Clinical manifestation consisting of a deficiency of carbon dioxide in arterial blood. [NIH] Hypoglycaemia: An abnormally diminished concentration of glucose in the blood, which may lead to tremulousness, cold sweat, piloerection, hypothermia, and headache, accompanied by irritability, confusion, hallucinations, bizarre behaviour, and ultimately, convulsions and coma. [EU] Hypokalaemia: Abnormally low potassium concentration in the blood; it may result from potassium loss by renal secretion or by the gastrointestinal route, as by vomiting or diarrhoea. It may be manifested clinically by neuromuscular disorders ranging from weakness to paralysis, by electrocardiographic abnormalities (depression of the T wave and elevation of the U wave), by renal disease, and by gastrointestinal disorders. [EU] Hypotension: Abnormally low blood pressure. [NIH] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypothermia: Lower than normal body temperature, especially in warm-blooded animals; in man usually accidental or unintentional. [NIH] Hypotonic Solutions: Solutions that have a lesser osmotic pressure than a reference solution such as blood, plasma, or interstitial fluid. [NIH] Hypovolemia: An abnormally low volume of blood circulating through the body. It may result in hypovolemic shock. [NIH] Hypoxemia: Deficient oxygenation of the blood; hypoxia. [EU] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Hypoxic: Having too little oxygen. [NIH] Iatrogenic: Resulting from the activity of physicians. Originally applied to disorders induced in the patient by autosuggestion based on the physician's examination, manner, or discussion, the term is now applied to any adverse condition in a patient occurring as the result of treatment by a physician or surgeon, especially to infections acquired by the patient during the course of treatment. [EU] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU]

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Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incidental: 1. Small and relatively unimportant, minor; 2. Accompanying, but not a major part of something; 3. (To something) Liable to occur because of something or in connection with something (said of risks, responsibilities, .) [EU] Incision: A cut made in the body during surgery. [NIH] Incisional: The removal of a sample of tissue for examination under a microscope. [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Incubation period: The period of time likely to elapse between exposure to the agent of the disease and the onset of clinical symptoms. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indocyanine Green: A tricarbocyanine dye that is used diagnostically in liver function tests and to determine blood volume and cardiac output. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease.

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[EU]

Infectious Diarrhea: Diarrhea caused by infection from bacteria, viruses, or parasites. [NIH] Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]

Informed Consent: Voluntary authorization, given to the physician by the patient, with full comprehension of the risks involved, for diagnostic or investigative procedures and medical and surgical treatment. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inguinal: Pertaining to the inguen, or groin. [EU] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insomnia: Difficulty in going to sleep or getting enough sleep. [NIH] Insufflation: The act of blowing a powder, vapor, or gas into any body cavity for experimental, diagnostic, or therapeutic purposes. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant monitoring. It is usually administered in specially equipped units of a health care facility. [NIH]

Intensive Care Units: Hospital units providing continuous surveillance and care to acutely ill patients. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU]

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Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intraindividual: Being or occurring within the individual. [EU] Intramuscular: IM. Within or into muscle. [NIH] Intravascular: Within a vessel or vessels. [EU] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Intubation: Introduction of a tube into a hollow organ to restore or maintain patency if obstructed. It is differentiated from catheterization in that the insertion of a catheter is usually performed for the introducing or withdrawing of fluids from the body. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ion Exchange: Reversible chemical reaction between a solid, often an ION exchange resin, and a fluid whereby ions may be exchanged from one substance to another. This technique is used in water purification, in research, and in industry. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Iontophoresis: Therapeutic introduction of ions of soluble salts into tissues by means of electric current. In medical literature it is commonly used to indicate the process of increasing the penetration of drugs into surface tissues by the application of electric current. It has nothing to do with ion exchange, air ionization nor phonophoresis, none of which requires current. [NIH] Ipsilateral: Having to do with the same side of the body. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction

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of a blood vessel. [EU] Isoproterenol: Isopropyl analog of epinephrine; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Ketoacidosis: Acidosis accompanied by the accumulation of ketone bodies (ketosis) in the body tissues and fluids, as in diabetic acidosis. [EU] Ketone Bodies: Chemicals that the body makes when there is not enough insulin in the blood and it must break down fat for its energy. Ketone bodies can poison and even kill body cells. When the body does not have the help of insulin, the ketones build up in the blood and then "spill" over into the urine so that the body can get rid of them. The body can also rid itself of one type of ketone, called acetone, through the lungs. This gives the breath a fruity odor. Ketones that build up in the body for a long time lead to serious illness and coma. [NIH] Ketosis: A condition of having ketone bodies build up in body tissues and fluids. The signs of ketosis are nausea, vomiting, and stomach pain. Ketosis can lead to ketoacidosis. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Language Development: The gradual expansion in complexity and meaning of symbols and sounds as perceived and interpreted by the individual through a maturational and learning process. Stages in development include babbling, cooing, word imitation with cognition, and use of short sentences. [NIH] Laparoscopy: Examination, therapy or surgery of the abdomen's interior by means of a laparoscope. [NIH] Laparotomy: A surgical incision made in the wall of the abdomen. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Leg Ulcer: Ulceration of the skin and underlying structures of the lower extremity. About 90% of the cases are due to venous insufficiency (varicose ulcer), 5% to arterial disease, and

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the remaining 5% to other causes. [NIH] Lentivirus: A genus of the family Retroviridae consisting of non-oncogenic retroviruses that produce multi-organ diseases characterized by long incubation periods and persistent infection. Lentiviruses are unique in that they contain open reading frames (ORFs) between the pol and env genes and in the 3' env region. Five serogroups are recognized, reflecting the mammalian hosts with which they are associated. HIV-1 is the type species. [NIH] Leprosy: A chronic granulomatous infection caused by Mycobacterium leprae. The granulomatous lesions are manifested in the skin, the mucous membranes, and the peripheral nerves. Two polar or principal types are lepromatous and tuberculoid. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukocytosis: A transient increase in the number of leukocytes in a body fluid. [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Levofloxacin: A substance used to treat bacterial infections. It belongs to the family of drugs called quinolone antibiotics. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. [NIH] Life Expectancy: A figure representing the number of years, based on known statistics, to which any person of a given age may reasonably expect to live. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Liminal: The main auxiliary method for diagnosing impairment of hearing and determining its localization. Routine tests are carried out within the register of frequencies 125 to 8000 Hz. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Linkage Disequilibrium: Nonrandom association of linked genes. This is the tendency of the alleles of two separate but already linked loci to be found together more frequently than would be expected by chance alone. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an

Dictionary 289

electron acceptor. [NIH] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Locomotor: Of or pertaining to locomotion; pertaining to or affecting the locomotive apparatus of the body. [EU] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lumen: The cavity or channel within a tube or tubular organ. [EU] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Maintenance therapy: Treatment that is given to help a primary (original) treatment keep working. Maintenance therapy is often given to help keep cancer in remission. [NIH]

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Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malaise: A vague feeling of bodily discomfort. [EU] Malaria: A protozoan disease caused in humans by four species of the genus Plasmodium (P. falciparum (malaria, falciparum), P. vivax (malaria, vivax), P. ovale, and P. malariae) and transmitted by the bite of an infected female mosquito of the genus Anopheles. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high fever, sweating, shaking chills, and anemia. Malaria in animals is caused by other species of plasmodia. [NIH] Malaria, Falciparum: Malaria caused by Plasmodium falciparum. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations. [NIH] Malaria, Vivax: Malaria caused by Plasmodium vivax. This form of malaria is less severe than malaria, falciparum, but there is a higher probability for relapses to occur. Febrile paroxysms often occur every other day. [NIH] Malformation: A morphologic developmental process. [EU]

defect

resulting

from

an

intrinsically

abnormal

Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mammary: Pertaining to the mamma, or breast. [EU] Manic: Affected with mania. [EU] Manic-depressive psychosis: One of a group of psychotic reactions, fundamentally marked by severe mood swings and a tendency to remission and recurrence. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Maternal-Fetal Exchange: Exchange of substances between the maternal blood and the fetal blood through the placental barrier. It excludes microbial or viral transmission. [NIH] Meatus: A canal running from the internal auditory foramen through the petrous portion of the temporal bone. It gives passage to the facial and auditory nerves together with the auditory branch of the basilar artery and the internal auditory veins. [NIH] Mechanical ventilation: Use of a machine called a ventilator or respirator to improve the exchange of air between the lungs and the atmosphere. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve

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or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Megacolon: Pathological enlargement of the colon. [NIH] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mercaptopurine: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU] Mesentery: A layer of the peritoneum which attaches the abdominal viscera to the abdominal wall and conveys their blood vessels and nerves. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in

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the original (primary) tumor. The plural is metastases. [NIH] Metoclopramide: A dopamine D2 antagonist that is used as an antiemetic. [NIH] Metronidazole: Antiprotozoal used in amebiasis, trichomoniasis, giardiasis, and as treponemacide in livestock. It has also been proposed as a radiation sensitizer for hypoxic cells. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985, p133), this substance may reasonably be anticipated to be a carcinogen (Merck, 11th ed). [NIH] Mexiletine: Antiarrhythmic agent pharmacologically similar to lidocaine. It may have some anticonvulsant properties. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Midodrine: An ethanolamine derivative that is an adrenergic alpha agonist. It is used as a vasoconstrictor agent in the treatment of hypotension. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mitogen-Activated Protein Kinase Kinases: A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate mitogen-activated protein kinases and are themselves phosphorylated by MAP kinase kinase kinases. JNK kinases (also known as SAPK kinases) are a subfamily. EC 2.7.10.- [NIH] Mitogen-Activated Protein Kinases: A superfamily of protein-serine-threonine kinases that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by mitogen-activated protein kinase kinases which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP kinase kinase kinases). Families of these mitogen-activated protein kinases (MAPKs) include extracellular signal-regulated kinases (ERKs), stress-activated protein kinases (SAPKs) (also known as c-jun terminal kinases (JNKs)), and p38-mitogen-activated protein kinases. EC 2,7,1.- [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which

Dictionary 293

the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]

Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Probes: A group of atoms or molecules attached to other molecules or cellular structures and used in studying the properties of these molecules and structures. Radioactive DNA or RNA sequences are used in molecular genetics to detect the presence of a complementary sequence by molecular hybridization. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monogenic: A human disease caused by a mutation in a single gene. [NIH] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Mouth Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Mucinous: Containing or resembling mucin, the main compound in mucus. [NIH] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multicenter Studies: Controlled studies which are planned and carried out by several cooperating institutions to assess certain variables and outcomes in specific patient populations, for example, a multicenter study of congenital anomalies in children. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]

Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH]

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Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Musculature: The muscular apparatus of the body, or of any part of it. [EU] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myocardial Contraction: Contractile activity of the heart. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary arteriosclerosis), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (myocardial infarction). [NIH] Myocardial Reperfusion: Generally, restoration of blood supply to heart tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. Reperfusion can be induced to treat ischemia. Methods include chemical dissolution of an occluding thrombus, administration of vasodilator drugs, angioplasty, catheterization, and artery bypass graft surgery. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing myocardial reperfusion injury. [NIH] Myocardial Reperfusion Injury: Functional, metabolic, or structural changes in ischemic heart muscle thought to result from reperfusion to the ischemic areas. Changes can be fatal to muscle cells and may include edema with explosive cell swelling and disintegration, sarcolemma disruption, fragmentation of mitochondria, contraction band necrosis, enzyme washout, and calcium overload. Other damage may include hemorrhage and ventricular arrhythmias. One possible mechanism of damage is thought to be oxygen free radicals. Treatment currently includes the introduction of scavengers of oxygen free radicals, and injury is thought to be prevented by warm blood cardioplegic infusion prior to reperfusion. [NIH]

Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myofibrils: Highly organized bundles of actin, myosin, and other proteins in the cytoplasm of skeletal and cardiac muscle cells that contract by a sliding filament mechanism. [NIH] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Narcolepsy: A condition of unknown cause characterized by a periodic uncontrollable tendency to fall asleep. [NIH] Narcosis: A general and nonspecific reversible depression of neuronal excitability, produced by a number of physical and chemical aspects, usually resulting in stupor. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit.

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Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neonatal Abstinence Syndrome: Fetal and neonatal addiction and withdrawal as a result of the mother's dependence on drugs during pregnancy. Withdrawal or abstinence symptoms develop shortly after birth. Symptoms exhibited are loud, high-pitched crying, sweating, yawning and gastrointestinal disturbances. [NIH] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephron: A tiny part of the kidneys. Each kidney is made up of about 1 million nephrons, which are the working units of the kidneys, removing wastes and extra fluids from the blood. [NIH] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nerve Growth Factor: Nerve growth factor is the first of a series of neurotrophic factors that were found to influence the growth and differentiation of sympathetic and sensory neurons. It is comprised of alpha, beta, and gamma subunits. The beta subunit is responsible for its growth stimulating activity. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Nervousness: Excessive excitability and irritability, with mental and physical unrest. [EU] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neural Crest: A strip of specialized ectoderm flanking each side of the embryonal neural plate, which after the closure of the neural tube, forms a column of isolated cells along the dorsal aspect of the neural tube. Most of the cranial and all of the spinal sensory ganglion cells arise by differentiation of neural crest cells. [NIH] Neural Pathways: Neural tracts connecting one part of the nervous system with another. [NIH]

Neuritis: A general term indicating inflammation of a peripheral or cranial nerve. Clinical manifestation may include pain; paresthesias; paresis; or hypesthesia. [NIH] Neurogenic: Loss of bladder control caused by damage to the nerves controlling the bladder. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH]

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Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [NIH] Niacinamide: An important compound functioning as a component of the coenzyme NAD. Its primary significance is in the prevention and/or cure of blacktongue and pellagra. Most animals cannot manufacture this compound in amounts sufficient to prevent nutritional deficiency and it therefore must be supplemented through dietary intake. [NIH] Nicorandil: A derivative of the niacinamide that is structurally combined with an organic nitrate. It is a potassium-channel opener that causes vasodilatation of arterioles and large coronary arteries. Its nitrate-like properties produce venous vasodilation through stimulation of guanylate cyclase. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH]

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Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Open Reading Frames: Reading frames where successive nucleotide triplets can be read as codons specifying amino acids and where the sequence of these triplets is not interrupted by stop codons. [NIH] Opiate: A remedy containing or derived from opium; also any drug that induces sleep. [EU] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Orderly: A male hospital attendant. [NIH] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Orthostatic: Pertaining to or caused by standing erect. [EU] Osmolarity: The concentration of osmotically active particles expressed in terms of osmoles of solute per litre of solution. [EU] Osmoles: The standard unit of osmotic pressure. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Ouabain: A cardioactive glycoside consisting of rhamnose and ouabagenin, obtained from the seeds of Strophanthus gratus and other plants of the Apocynaceae; used like digitalis. It is commonly used in cell biological studies as an inhibitor of the NA(+)-K(+)-exchanging atpase. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Overexpress: An excess of a particular protein on the surface of a cell. [NIH] Overweight: An excess of body weight but not necessarily body fat; a body mass index of 25

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to 29.9 kg/m2. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxalate: A chemical that combines with calcium in urine to form the most common type of kidney stone (calcium oxalate stone). [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Pacemaker: An object or substance that influences the rate at which a certain phenomenon occurs; often used alone to indicate the natural cardiac pacemaker or an artificial cardiac pacemaker. In biochemistry, a substance whose rate of reaction sets the pace for a series of interrelated reactions. [EU] Pacer: Device that delivers battery-supplied electrical stimuli over leads with electrodes in contact with the heart. Virtually all leads are inserted transvenously. Electronic circuitry regulates the timing and characteristics of the stimuli. [NIH] Paediatric: Of or relating to the care and medical treatment of children; belonging to or concerned with paediatrics. [EU] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pallor: A clinical manifestation consisting of an unnatural paleness of the skin. [NIH] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Panic Disorder: A type of anxiety disorder characterized by unexpected panic attacks that last minutes or, rarely, hours. Panic attacks begin with intense apprehension, fear or terror

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and, often, a feeling of impending doom. Symptoms experienced during a panic attack include dyspnea or sensations of being smothered; dizziness, loss of balance or faintness; choking sensations; palpitations or accelerated heart rate; shakiness; sweating; nausea or other form of abdominal distress; depersonalization or derealization; paresthesias; hot flashes or chills; chest discomfort or pain; fear of dying and fear of not being in control of oneself or going crazy. Agoraphobia may also develop. Similar to other anxiety disorders, it may be inherited as an autosomal dominant trait. [NIH] Papaverine: An alkaloid found in opium but not closely related to the other opium alkaloids in its structure or pharmacological actions. It is a direct-acting smooth muscle relaxant used in the treatment of impotence and as a vasodilator, especially for cerebral vasodilation. The mechanism of its pharmacological actions is not clear, but it apparently can inhibit phosphodiesterases and it may have direct actions on calcium channels. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Parasympathetic Nervous System: The craniosacral division of the autonomic nervous system. The cell bodies of the parasympathetic preganglionic fibers are in brain stem nuclei and in the sacral spinal cord. They synapse in cranial autonomic ganglia or in terminal ganglia near target organs. The parasympathetic nervous system generally acts to conserve resources and restore homeostasis, often with effects reciprocal to the sympathetic nervous system. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Paresis: A general term referring to a mild to moderate degree of muscular weakness, occasionally used as a synonym for paralysis (severe or complete loss of motor function). In the older literature, paresis often referred specifically to paretic neurosyphilis. "General paresis" and "general paralysis" may still carry that connotation. Bilateral lower extremity paresis is referred to as paraparesis. [NIH] Paresthesias: Abnormal touch sensations, such as burning or prickling, that occur without an outside stimulus. [NIH] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Parturition: The act or process of given birth to a child. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologies: The study of abnormality, especially the study of diseases. [NIH]

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Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peptic Ulcer: An ulceration of the mucous membrane of the esophagus, stomach or duodenum, caused by the action of the acid gastric juice. [NIH] Peptic Ulcer Hemorrhage: Bleeding from a peptic ulcer. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Perioperative: Around the time of surgery; usually lasts from the time of going into the hospital or doctor's office for surgery until the time the patient goes home. [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneal Dialysis: Dialysis fluid being introduced into and removed from the peritoneal cavity as either a continuous or an intermittent procedure. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Peroneal Nerve: The lateral of the two terminal branches of the sciatic nerve. The peroneal (or fibular) nerve provides motor and sensory innervation to parts of the leg and foot. [NIH] Perspiration: Sweating; the functional secretion of sweat. [EU] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity

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increases and below it acidity increases. [EU] Pharmacodynamics: The study of the biochemical and physiological effects of drugs and the mechanisms of their actions, including the correlation of actions and effects of drugs with their chemical structure; also, such effects on the actions of a particular drug or drugs. [EU] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phonophoresis: Use of ultrasound to increase the percutaneous adsorption of drugs. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH]

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Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma Volume: Volume of plasma in the circulation. It is usually measured by indicator dilution techniques. [NIH] Plasmids: Any extrachromosomal hereditary determinant. Plasmids are self-replicating circular molecules of DNA that are found in a variety of bacterial, archaeal, fungal, algal, and plant species. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]

Pleomorphic: Occurring in various distinct forms. In terms of cells, having variation in the size and shape of cells or their nuclei. [NIH] Plethysmography: Recording of change in the size of a part as modified by the circulation in it. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Podophyllotoxin: The main active constituent of the resin from the roots of may apple or mandrake (Podophyllum peltatum and P. emodi). It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides,

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proteins, plastics). [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polyunsaturated fat: An unsaturated fat found in greatest amounts in foods derived from plants, including safflower, sunflower, corn, and soybean oils. [NIH] Pons: The part of the central nervous system lying between the medulla oblongata and the mesencephalon, ventral to the cerebellum, and consisting of a pars dorsalis and a pars ventralis. [NIH] Porphyria: A group of disorders characterized by the excessive production of porphyrins or their precursors that arises from abnormalities in the regulation of the porphyrin-heme pathway. The porphyrias are usually divided into three broad groups, erythropoietic, hepatic, and erythrohepatic, according to the major sites of abnormal porphyrin synthesis. [NIH]

Porphyrins: A group of compounds containing the porphin structure, four pyrrole rings connected by methine bridges in a cyclic configuration to which a variety of side chains are attached. The nature of the side chain is indicated by a prefix, as uroporphyrin, hematoporphyrin, etc. The porphyrins, in combination with iron, form the heme component in biologically significant compounds such as hemoglobin and myoglobin. [NIH] Port: An implanted device through which blood may be withdrawn and drugs may be infused without repeated needle sticks. Also called a port-a-cath. [NIH] Port-a-cath: An implanted device through which blood may be withdrawn and drugs may be infused without repeated needle sticks. Also called a port. [NIH] Post partum: After childbirth, or after delivery. [EU] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postoperative: After surgery. [NIH] Postoperative Period: The period following a surgical operation. [NIH] Postprandial: Occurring after dinner, or after a meal; postcibal. [EU] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Postural: Pertaining to posture or position. [EU] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potassium Channels: Cell membrane glycoproteins selective for potassium ions. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH]

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Preclinical: Before a disease becomes clinically recognizable. [EU] Precordial: Pertaining to the precordium (= region over the heart and lower part of the thorax). [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Pre-Eclampsia: Development of hypertension with proteinuria, edema, or both, due to pregnancy or the influence of a recent pregnancy. It occurs after the 20th week of gestation, but it may develop before this time in the presence of trophoblastic disease. [NIH] Pre-eclamptic: A syndrome characterized by hypertension, albuminuria, and generalized oedema, occurring only in pregnancy. [NIH] Pre-Excitation Syndromes: Conditions characterized by activation of the whole or some part of the ventricle by the atrial impulse earlier than would be expected if the impulse reached the ventricle by way of the normal specific conduction system only. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Prenatal Diagnosis: Determination of the nature of a pathological condition or disease in the postimplantation embryo, fetus, or pregnant female before birth. [NIH] Preoperative: Preceding an operation. [EU] Pressoreceptors: Receptors in the vascular system, particularly the aorta and carotid sinus, which are sensitive to stretch of the vessel walls. [NIH] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Priapism: Persistent abnormal erection of the penis, usually without sexual desire, and accompanied by pain and tenderness. It is seen in diseases and injuries of the spinal cord, and may be caused by vesical calculus and certain injuries to the penis. [EU] Primary endpoint: The main result that is measured at the end of a study to see if a given treatment worked (e.g., the number of deaths or the difference in survival between the treatment group and the control group). What the primary endpoint will be is decided before the study begins. [NIH] Primary Prevention: Prevention of disease or mental disorders in susceptible individuals or populations through promotion of health, including mental health, and specific protection, as in immunization, as distinguished from the prevention of complications or after-effects of existing disease. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [NIH] Proctitis: Inflammation of the rectum. [EU] Proctosigmoiditis: Irritation of the rectum and the sigmoid colon. [NIH]

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Proctosigmoidoscopy: An examination of the rectum and the lower part of the colon using a thin, lighted tube called a sigmoidoscope. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prone: Having the front portion of the body downwards. [NIH] Prone Position: The posture of an individual lying face down. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Propofol: A widely used anesthetic. [NIH] Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol is used in the treatment or prevention of many disorders including acute myocardial infarction, arrhythmias, angina pectoris, hypertension, hypertensive emergencies, hyperthyroidism, migraine, pheochromocytoma, menopause, and anxiety. [NIH] Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also).

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The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Prosthesis: An artificial replacement of a part of the body. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Kinase C: An enzyme that phosphorylates proteins on serine or threonine residues in the presence of physiological concentrations of calcium and membrane phospholipids. The additional presence of diacylglycerols markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by phorbol esters and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. EC 2.7.1.-. [NIH] Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors. EC 2.7.10. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoan: 1. Any individual of the protozoa; protozoon. 2. Of or pertaining to the protozoa; protozoal. [EU] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritic: Pertaining to or characterized by pruritus. [EU]

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Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Psychogenic: Produced or caused by psychic or mental factors rather than organic factors. [EU]

Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychosis: A mental disorder characterized by gross impairment in reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behaviour without apparent awareness on the part of the patient of the incomprehensibility of his behaviour; the term is also used in a more general sense to refer to mental disorders in which mental functioning is sufficiently impaired as to interfere grossly with the patient's capacity to meet the ordinary demands of life. Historically, the term has been applied to many conditions, e.g. manic-depressive psychosis, that were first described in psychotic patients, although many patients with the disorder are not judged psychotic. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Circulation: The circulation of blood through the lungs. [NIH] Pulmonary congestion: Fluid accumulation in the lungs. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulmonary Valve: A valve situated at the entrance to the pulmonary trunk from the right ventricle. [NIH] Pulmonary Veins: The veins that return the oxygenated blood from the lungs to the left atrium of the heart. [NIH] Pulsation: A throb or rhythmical beat, as of the heart. [EU] Pulse: The rhythmical expansion and contraction of an artery produced by waves of

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pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Pupil: The aperture in the iris through which light passes. [NIH] Pustular: Pertaining to or of the nature of a pustule; consisting of pustules (= a visible collection of pus within or beneath the epidermis). [EU] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quinidine: An optical isomer of quinine, extracted from the bark of the Cinchona tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular action potential, and decreases automaticity. Quinidine also blocks muscarinic and alphaadrenergic neurotransmission. [NIH] Quinine: An alkaloid derived from the bark of the cinchona tree. It is used as an antimalarial drug, and is the active ingredient in extracts of the cinchona that have been used for that purpose since before 1633. Quinine is also a mild antipyretic and analgesic and has been used in common cold preparations for that purpose. It was used commonly and as a bitter and flavoring agent, and is still useful for the treatment of babesiosis. Quinine is also useful in some muscular disorders, especially nocturnal leg cramps and myotonia congenita, because of its direct effects on muscle membrane and sodium channels. The mechanisms of its antimalarial effects are not well understood. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Racemic: Optically inactive but resolvable in the way of all racemic compounds. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radiofrequency ablation: The use of electrical current to destroy tissue. [NIH] Radiography: Examination of any part of the body for diagnostic purposes by means of roentgen rays, recording the image on a sensitized surface (such as photographic film). [NIH] Radioimmunoassay: Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Nonimmunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH]

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Radionuclide Imaging: Process whereby a radionuclide is injected or measured (through tissue) from an external source, and a display is obtained from any one of several rectilinear scanner or gamma camera systems. The image obtained from a moving detector is called a scan, while the image obtained from a stationary camera device is called a scintiphotograph. [NIH]

Radionuclide Ventriculography: Imaging of a ventricle of the heart after the injection of a radioactive contrast medium. The technique is less invasive than cardiac catheterization and is used to assess ventricular function. [NIH] Radiopharmaceutical: Any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. [NIH] Randomization: Also called random allocation. Is allocation of individuals to groups, e.g., for experimental and control regimens, by chance. Within the limits of chance variation, random allocation should make the control and experimental groups similar at the start of an investigation and ensure that personal judgment and prejudices of the investigator do not influence allocation. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Reactivation: The restoration of activity to something that has been inactivated. [EU] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Reality Testing: The individual's objective evaluation of the external world and the ability to differentiate adequately between it and the internal world; considered to be a primary ego function. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU]

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Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reentry: Reexcitation caused by continuous propagation of the same impulse for one or more cycles. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflective: Capable of throwing back light, images, sound waves : reflecting. [EU] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Registries: The systems and processes involved in the establishment, support, management, and operation of registers, e.g., disease registers. [NIH] Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]

Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. [NIH] Reperfusion Injury: Functional, metabolic, or structural changes, including necrosis, in ischemic tissues thought to result from reperfusion to ischemic areas of the tissue. The most

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common instance is myocardial reperfusion injury. [NIH] Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [NIH] Research Support: Financial support of research activities. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respirator: A mechanical device that helps a patient breathe; a mechanical ventilator. [NIH] Respiratory failure: Inability of the lungs to conduct gas exchange. [NIH] Respiratory Physiology: Functions and activities of the respiratory tract as a whole or of any of its parts. [NIH] Restitution: The restoration to a normal state. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Restrictive cardiomyopathy: Heart muscle disease in which the muscle walls become stiff and lose their flexibility. [NIH] Resuscitation: The restoration to life or consciousness of one apparently dead; it includes such measures as artificial respiration and cardiac massage. [EU] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinoids: Derivatives of vitamin A. Used clinically in the treatment of severe cystic acne, psoriasis, and other disorders of keratinization. Their possible use in the prophylaxis and treatment of cancer is being actively explored. [NIH] Retreatment: The therapy of the same disease in a patient, with the same agent or procedure repeated after initial treatment, or with an additional or alternate measure or follow-up. It does not include therapy which requires more than one administration of a therapeutic agent or regimen. Retreatment is often used with reference to a different modality when the original one was inadequate, harmful, or unsuccessful. [NIH] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Retroperitoneal: Having to do with the area outside or behind the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective Studies: Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Reversion: A return to the original condition, e. g. the reappearance of the normal or wild type in previously mutated cells, tissues, or organisms. [NIH] Rhamnose: A methylpentose whose L- isomer is found naturally in many plant glycosides

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and some gram-negative bacterial lipopolysaccharides. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Rod: A reception for vision, located in the retina. [NIH] Rubber: A high-molecular-weight polymeric elastomer derived from the milk juice (latex) of Hevea brasiliensis and other trees. It is a substance that can be stretched at room temperature to atleast twice its original length and after releasing the stress, retractrapidly, and recover its original dimensions fully. Synthetic rubber is made from many different chemicals, including styrene, acrylonitrile, ethylene, propylene, and isoprene. [NIH] Saline: A solution of salt and water. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Saphenous: Applied to certain structures in the leg, e. g. nerve vein. [NIH] Saphenous Vein: The vein which drains the foot and leg. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Sarcoid: A cutaneus lesion occurring as a manifestation of sarcoidosis. [NIH] Sarcoidosis: An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands. [NIH] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [NIH] Sarcoplasmic Reticulum: A network of tubules and sacs in the cytoplasm of skeletal muscles that assist with muscle contraction and relaxation by releasing and storing calcium ions. [NIH] Scalpel: A small pointed knife with a convex edge. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of

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thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sciatic Nerve: A nerve which originates in the lumbar and sacral spinal cord (L4 to S3) and supplies motor and sensory innervation to the lower extremity. The sciatic nerve, which is the main continuation of the sacral plexus, is the largest nerve in the body. It has two major branches, the tibial nerve and the peroneal nerve. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Sclerotherapy: Treatment of varicose veins, hemorrhoids, gastric and esophageal varices, and peptic ulcer hemorrhage by injection or infusion of chemical agents which cause localized thrombosis and eventual fibrosis and obliteration of the vessels. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Sedentary: 1. Sitting habitually; of inactive habits. 2. Pertaining to a sitting posture. [EU] Sediment: A precipitate, especially one that is formed spontaneously. [EU] Sedimentation: The act of causing the deposit of sediment, especially by the use of a centrifugal machine. [EU] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senescence: The bodily and mental state associated with advancing age. [NIH] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [NIH] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septal: An abscess occurring at the root of the tooth on the proximal surface. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Septicemia: Systemic disease associated with the presence and persistence of pathogenic microorganisms or their toxins in the blood. Called also blood poisoning. [EU]

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Septum: A dividing wall or partition; a general term for such a structure. The term is often used alone to refer to the septal area or to the septum pellucidum. [EU] Septum Pellucidum: A triangular double membrane separating the anterior horns of the lateral ventricles of the brain. It is situated in the median plane and bounded by the corpus callosum and the body and columns of the fornix. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Sigmoid: 1. Shaped like the letter S or the letter C. 2. The sigmoid colon. [EU] Sigmoid Colon: The lower part of the colon that empties into the rectum. [NIH] Sigmoidoscope: A thin, lighted tube used to view the inside of the colon. [NIH] Sigmoidoscopy: Endoscopic examination, therapy or surgery of the sigmoid flexure. [NIH] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by

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a physician, or subjective when perceived by the patient. [NIH] Sinoatrial Node: The small mass of modified cardiac muscle fibers located at the junction of the superior vena cava and right atrium. Contraction impulses probably start in this node, spread over the atrium and are then transmitted by the atrioventricular bundle to the ventricle. [NIH] Sinusal: Pertaining to the sinus. [EU] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sleep apnea: A serious, potentially life-threatening breathing disorder characterized by repeated cessation of breathing due to either collapse of the upper airway during sleep or absence of respiratory effort. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smoking Cessation: Discontinuation of the habit of smoking, the inhaling and exhaling of tobacco smoke. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Soaps: Sodium or potassium salts of long chain fatty acids. These detergent substances are obtained by boiling natural oils or fats with caustic alkali. Sodium soaps are harder and are used as topical anti-infectives and vehicles in pills and liniments; potassium soaps are soft, used as vehicles for ointments and also as topical antimicrobials. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solitary Nucleus: Gray matter located in the dorsomedial part of the medulla oblongata associated with the solitary tract. The solitary nucleus receives inputs from most organ systems including the terminations of the facial, glossopharyngeal, and vagus nerves. It is a major coordinator of autonomic nervous system regulation of cardiovascular, respiratory, gustatory, gastrointestinal, and chemoreceptive aspects of homeostasis. The solitary nucleus is also notable for the large number of neurotransmitters which are found therein. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatic cells: All the body cells except the reproductive (germ) cells. [NIH]

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Sotalol: An adrenergic beta-antagonist that is used in the treatment of life-threatening arrhythmias. [NIH] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Soybean Oil: Oil from soybean or soybean plant. [NIH] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrin: A high molecular weight (220-250 kDa) water-soluble protein which can be extracted from erythrocyte ghosts in low ionic strength buffers. The protein contains no lipids or carbohydrates, is the predominant species of peripheral erythrocyte membrane proteins, and exists as a fibrous coating on the inner, cytoplasmic surface of the membrane. [NIH]

Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Stabilization: The creation of a stable state. [EU] Standard therapy: A currently accepted and widely used treatment for a certain type of cancer, based on the results of past research. [NIH] Statistically significant: Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. [NIH] Steady state: Dynamic equilibrium. [EU] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stellate: Star shaped. [NIH] Stellate Ganglion: A paravertebral sympathetic ganglion formed by the fusion of the

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inferior cervical and first thoracic ganglia. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stroke Volume: The amount of blood pumped out of the heart per beat not to be confused with cardiac output (volume/time). [NIH] Stump: The end of the limb after amputation. [NIH] Stupor: Partial or nearly complete unconsciousness, manifested by the subject's responding only to vigorous stimulation. Also, in psychiatry, a disorder marked by reduced responsiveness. [EU] Styrene: A colorless, toxic liquid with a strong aromatic odor. It is used to make rubbers, polymers and copolymers, and polystyrene plastics. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclavian: The direct continuation of the axillary vein at the lateral border of the first rib. It passes medially to join the internal jugular vein and form the brachiocephalic vein on each side. [NIH] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions

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of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Sudden cardiac death: Cardiac arrest caused by an irregular heartbeat. [NIH] Sudden death: Cardiac arrest caused by an irregular heartbeat. The term "death" is somewhat misleading, because some patients survive. [NIH] Superior vena cava: Vein which returns blood from the head and neck, upper limbs, and thorax. It is formed by the union of the two brachiocephalic veins. [NIH] Supine: Having the front portion of the body upwards. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Supraventricular: Situated or occurring above the ventricles, especially in an atrium or atrioventricular node. [EU] Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods. [NIH] Sympathectomy: The removal or interruption of some part of the sympathetic nervous system for therapeutic or research purposes. [NIH] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU]

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Synchrony: The normal physiologic sequencing of atrial and ventricular activation and contraction. [NIH] Syncope: A temporary suspension of consciousness due to generalized cerebral schemia, a faint or swoon. [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Systole: Period of contraction of the heart, especially of the ventricles. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Systolic blood pressure: The maximum pressure in the artery produced as the heart contracts and blood begins to flow. [NIH] Systolic heart failure: Inability of the heart to contract with enough force to pump adequate amounts of blood through the body. [NIH] Tachyarrhythmia: Tachycardia associated with an irregularity in the normal heart rhythm. [EU]

Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tachycardia, Supraventricular: A generic expression for any tachycardia that originates above the bundle of His. [NIH] Tachycardia, Ventricular: An abnormally rapid ventricular rhythm with wide QRS complexes, usually in excess of 150 per minute. It is generated within the ventricle, below the Bundle of His, and is most commonly associated with atrioventricular dissociation. [NIH] Tachypnea: Rapid breathing. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Telecommunications: Transmission of information over distances via electronic means. [NIH]

Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Tendon: A discrete band of connective tissue mainly composed of parallel bundles of collagenous fibers by which muscles are attached, or two muscles bellies joined. [NIH] Tenesmus: Straining, especially ineffectual and painful straining at stool or in urination. [EU] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Theophylline: Alkaloid obtained from Thea sinensis (tea) and others. It stimulates the heart and central nervous system, dilates bronchi and blood vessels, and causes diuresis. The drug is used mainly in bronchial asthma and for myocardial stimulation. Among its more

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prominent cellular effects are inhibition of cyclic nucleotide phosphodiesterases and antagonism of adenosine receptors. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thoracic: Having to do with the chest. [NIH] Thoracotomy: Surgical incision into the chest wall. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thromboembolism: Obstruction of a vessel by a blood clot that has been transported from a distant site by the blood stream. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH]

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Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonicity: The normal state of muscular tension. [NIH] Tonus: A state of slight tension usually present in muscles even when they are not undergoing active contraction. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Torsades de Pointes: A ventricular tachycardia characterized by periodic twisting of the points of the QRS complexes and rates between 200 and 250 beats per minute. It may be selflimited or may progress to ventricular fibrillation. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicokinetics: Study of the absorption, distribution, metabolism, and excretion of test substances. [NIH] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Traction: The act of pulling. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transillumination: Passage of light through body tissues or cavities for examination of internal structures. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH]

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Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Trichomoniasis: An infection with the protozoan parasite Trichomonas vaginalis. [NIH] Tropomyosin: A protein found in the thin filaments of muscle fibers. It inhibits contraction of the muscle unless its position is modified by troponin. [NIH] Troponin: One of the minor protein components of skeletal muscle. Its function is to serve as the calcium-binding component in the troponin-tropomyosin B-actin-myosin complex by conferring calcium sensitivity to the cross-linked actin and myosin filaments. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Unsaturated Fats: A type of fat. [NIH] Uraemia: 1. An excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acids metabolism; more correctly referred to as azotemia. 2. In current usage the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting anorexia, a metallic taste in the mouth, a uraemic odour of the breath, pruritus, uraemic frost on the skin, neuromuscular disorders, pain and twitching in the muscles, hypertension, edema, mental confusion, and acid-base and electrolyte imbalances. [EU]

Urethane: Antineoplastic agent that is also used as a veterinary anesthetic. It has also been used as an intermediate in organic synthesis. Urethane is suspected to be a carcinogen. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

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Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary Retention: Inability to urinate. The etiology of this disorder includes obstructive, neurogenic, pharmacologic, and psychogenic causes. [NIH] Urinate: To release urine from the bladder to the outside. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urticaria: A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress. [NIH] Uterine Contraction: Contraction of the uterine muscle. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vagal: Pertaining to the vagus nerve. [EU] Vagotonia: Hyperexcitability of the vagus nerve; a condition in which the vagus nerve dominates in the general functioning of the body organs. It is marked by vasomotor instability, constipation, sweating, and involuntary motor spasms with pain. [EU] Vagus Nerve: The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). [NIH] Valves: Flap-like structures that control the direction of blood flow through the heart. [NIH] Varicose: The common ulcer in the lower third of the leg or near the ankle. [NIH] Varicose Ulcer: Ulcer due to varicose veins. Chronic venous insufficiency in the deep veins of the legs leads to shunting the venous return into the superficial veins, in which pressure and flow rate, as well as oxygen content, are increased. [NIH] Varicose vein: An abnormal swelling and tortuosity especially of the superficial veins of the legs. [EU] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular endothelial growth factor: VEGF. A substance made by cells that stimulates new blood vessel formation. [NIH] Vascular Resistance: An expression of the resistance offered by the systemic arterioles, and to a lesser extent by the capillaries, to the flow of blood. [NIH] Vasculitis: Inflammation of a blood vessel. [NIH] Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilatation: A state of increased calibre of the blood vessels. [EU] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH]

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Vasomotor: 1. Affecting the calibre of a vessel, especially of a blood vessel. 2. Any element or agent that effects the calibre of a blood vessel. [EU] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Vena: A vessel conducting blood from the capillary bed to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Venous Pressure: The blood pressure in a vein. It is usually measured to assess the filling pressure to the ventricle. [NIH] Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU] Ventilator: A breathing machine that is used to treat respiratory failure by promoting ventilation; also called a respirator. [NIH] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Ventricular Dysfunction: A condition in which the ventricles of the heart exhibit a decreased functionality. [NIH] Ventricular fibrillation: Rapid, irregular quivering of the heart's ventricles, with no effective heartbeat. [NIH] Ventricular Function: The hemodynamic and electrophysiological action of the ventricles. [NIH]

Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertebral: Of or pertaining to a vertebra. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH]

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Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visceral Afferents: The sensory fibers innervating the viscera. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Wakefulness: A state in which there is an enhanced potential for sensitivity and an efficient responsiveness to external stimuli. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yawning: An involuntary deep inspiration with the mouth open, often accompanied by the act of stretching. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

327

INDEX 3 3-dimensional, 12, 28, 36, 56, 247 A Abdomen, 4, 45, 247, 257, 262, 263, 279, 286, 287, 289, 298, 300, 311, 316, 317, 320, 323 Abdominal, 4, 62, 94, 247, 291, 298, 299, 300, 311, 322 Abdominal Pain, 4, 247, 322 Abducens, 247, 249 Aberrant, 32, 247 Ablate, 24, 27, 89, 90, 247, 260, 272 Ablation, 11, 24, 27, 35, 41, 44, 49, 51, 56, 57, 64, 122, 138, 160, 187, 189, 215 Abscess, 3, 4, 247, 313 Acetylcholine, 13, 247, 262, 296 Acetylcholinesterase, 45, 247 Acidity, 247, 301 Acidosis, 18, 62, 247, 268, 287 Acne, 172, 247, 311 Acrylonitrile, 247, 312 Actin, 247, 293, 294, 322 Actinin, 247, 271 Action Potentials, 11, 20, 29, 37, 38, 50, 60, 247, 249 Adaptation, 45, 247 Adenine, 248 Adenosine, 9, 29, 68, 116, 117, 121, 123, 128, 130, 156, 184, 185 Adenosine Triphosphate, 100, 117, 248, 301 Adenylate Cyclase, 15, 184, 248 Adipose Tissue, 10, 248 Adjustment, 142, 146, 247, 248 Adolescence, 182, 248 Adrenal Cortex, 248, 305 Adrenal Medulla, 248, 260, 273, 274, 296 Adrenergic, 6, 14, 18, 29, 36, 52, 59, 62 Adrenergic Agonists, 6, 248 Adverse Effect, 5, 6, 248, 314 Aerobic, 248, 275 Afferent, 29, 46, 248 Affinity, 39, 248, 249, 315 Agar, 249, 302 Age of Onset, 249, 322 Aggressiveness, 175, 249 Agonist, 18, 108, 249, 270, 276, 292 Agranulocytosis, 172, 249

Airway, 9, 15, 249, 257, 315 Airway Resistance, 9, 249 Ajmaline, 118, 249 Albuterol, 124, 249 Alertness, 249, 258 Algorithms, 16, 20, 80, 155, 168, 183, 249, 256 Alimentary, 230, 249, 287, 299 Alkaline, 247, 249, 254, 258 Alkaloid, 249, 253, 293, 299, 308, 319 Alleles, 55, 249, 281, 282, 288 Alloys, 165, 166, 249 Alpha Particles, 249, 308 Alternans, 60, 103, 109, 112, 249 Alternative medicine, 121, 131, 195, 249 Alveoli, 250, 268, 324 Amebiasis, 250, 292 Amino acid, 250, 251, 252, 253, 279, 282, 297, 300, 301, 305, 306, 314, 317, 322 Amino Acid Sequence, 250, 251 Amiodarone, 23, 51, 65, 66, 67, 70, 76, 194, 199, 250 Ampulla, 250, 273 Amputation, 250, 317 Amygdala, 250, 255, 319 Amyloid, 166, 250, 279 Anaesthesia, 85, 103, 105, 107, 126, 250, 284 Analgesic, 250, 263, 293, 297, 308 Analog, 250, 287 Analogous, 16, 250, 321 Anatomical, 10, 20, 42, 51, 64, 250, 253, 262, 265, 269, 284, 313 Anemia, 209, 250, 280, 290 Anesthesia, 17, 72, 108, 109, 225, 232, 249, 250, 304 Anesthetics, 250, 274 Aneurysm, 98, 250, 277, 323 Angina, 9, 128, 129, 184, 219, 220, 222, 235, 251, 305 Angina Pectoris, 9, 235, 251, 305 Angioedema, 234, 251 Animal model, 17, 20, 32, 39, 43, 44, 47, 54, 56, 57, 58, 61, 251 Anions, 251, 286, 314 Anomalies, 251, 293, 319 Anorexia, 172, 251, 322 Antagonism, 251, 258, 269, 320

328

Tachycardia

Antianginal, 250, 251 Antiarrhythmic, 26, 38, 39, 49, 52, 56, 68, 100, 127, 181, 249, 250, 251, 292 Antibacterial, 251, 316 Antibiotic, 4, 29, 251, 257, 316 Antibodies, 6, 28, 58, 251, 254, 280, 281, 282, 284, 289, 302 Antibody, 65, 248, 251, 264, 267, 280, 282, 284, 291, 293, 308, 309, 316 Anticholinergic, 251, 269 Anticoagulant, 251, 306 Anticonvulsant, 251, 292 Antidepressant, 55, 251 Antiemetic, 251, 292 Antigen, 248, 251, 264, 278, 282, 284, 291, 308 Antihypertensive, 26, 252 Antimicrobial, 165, 252, 268 Antimitotic, 26, 252 Antioxidant, 44, 252, 253, 298 Antispasmodic, 252, 297 Antitussive, 252, 297 Anus, 252, 257, 263, 310 Anxiety, 55, 130, 229, 252, 298, 305 Anxiety Disorders, 252, 299 Aorta, 138, 140, 152, 188, 189, 252, 266, 304, 324 Aortic Valve, 104, 252 Apnea, 15, 34, 222, 252 Apolipoproteins, 252, 289 Aponeurosis, 252, 277 Aqueous, 199, 252, 255, 267 Arachidonic Acid, 8, 252, 288, 305 Arginine, 44, 252, 296 Aromatic, 157, 186, 252, 301, 317 Arrhythmogenic, 12, 36, 40, 41, 56, 66, 71, 85, 111, 252 Arrhythmogenic Right Ventricular Dysplasia, 66, 111, 252 Arterial, 5, 8, 18, 32, 46, 48, 58, 138, 181, 221, 252, 262, 282, 283, 287, 306, 319 Arteries, 66, 78, 92, 152, 188, 252, 256, 261, 265, 266, 289, 292, 294, 296, 307, 320 Arteriolar, 18, 252, 257 Arterioles, 252, 256, 258, 294, 296, 323 Arteriosus, 252, 307 Articular, 253, 297 Ascorbic Acid, 44, 253, 282 Aspartate, 117, 253 Asphyxia, 66, 79, 253 Assay, 28, 36, 59, 253, 308 Asymptomatic, 102, 250, 253, 277, 298

Asynchronous, 145, 253 Asystole, 34, 99, 149, 176, 253 Ataxia, 209, 253, 261, 319 Atrial Flutter, 11, 57, 70, 82, 89, 154, 163, 171, 175, 184, 188, 189, 218, 253 Atrial Function, 95, 253 Atrioventricular, 51, 66, 116, 118, 122, 123, 127, 133, 137, 138, 152, 154, 160, 168, 173 Atrioventricular Node, 51, 66, 79, 80, 82, 122, 173, 253, 318 Atrium, 12, 25, 138, 140, 144, 145, 152, 155, 159, 161, 171, 188 Atrophy, 208, 209, 253, 274 Atropine, 45, 79, 116, 181, 253, 255 Attenuated, 8, 15, 32, 43, 46, 253, 269 Attenuation, 15, 46, 59, 254 Atypical, 79, 123, 254 Auditory, 254, 290, 323 Autoantibodies, 254, 268 Autodigestion, 254, 298 Autonomic Dysreflexia, 221, 254 Autonomic Nervous System, 8, 23, 26, 29, 49, 178, 181, 182 Autonomic Neuropathy, 6, 38, 254 Autosuggestion, 254, 283 Axillary, 254, 317 Axillary Vein, 254, 317 B Bacteremia, 28, 254 Bacteria, 28, 251, 252, 254, 272, 273, 276, 279, 281, 285, 292, 309, 313, 316, 321, 323 Bacterial Infections, 254, 261, 288 Bacterial Physiology, 248, 254 Bactericidal, 254, 274 Bacteriophage, 254, 302, 321 Barium, 4, 254 Baroreflex, 8, 18, 46, 58, 86, 181, 254 Basal Ganglia, 253, 255, 277 Basal Ganglia Diseases, 253, 255 Base, 61, 117, 144, 152, 163, 169, 248, 255, 268, 277, 287, 319, 322 Basement Membrane, 255, 275 Basophils, 249, 255, 279, 288 Belladonna, 253, 255 Benign, 71, 154, 173, 255, 276, 277, 280, 295, 309 Beta-pleated, 250, 255 Bilateral, 29, 118, 255, 274, 299 Bile, 255, 277, 289, 317 Biliary, 255, 298 Biliary Tract, 255, 298 Bioavailability, 172, 255

329

Biochemical, 10, 62, 249, 255, 276, 297, 301, 314 Biological therapy, 255, 280 Biological Transport, 255, 269 Biopsy, 4, 7, 255, 300 Biotechnology, 65, 68, 195, 205, 207, 208, 209, 210, 256 Biotransformation, 256 Bipolar Disorder, 231, 256 Bladder, 254, 256, 264, 295, 306, 322, 323 Blastocyst, 256, 264, 301 Blood Cell Count, 28, 256, 280 Blood Coagulation, 256, 258, 320 Blood Flow Velocity, 18, 46, 256 Blood Glucose, 256, 281, 285 Blood Platelets, 256, 314 Blood Volume, 31, 46, 256, 284 Blood-Brain Barrier, 256, 281 Blot, 58, 256 Body Fluids, 256, 258, 271, 315 Body Mass Index, 256, 297 Bolus, 108, 256, 257 Bolus infusion, 256, 257 Bone Marrow, 257, 278, 283, 289 Bowel, 5, 7, 257, 285, 286, 300, 317, 322 Bowel Movement, 7, 257, 317 Brachiocephalic Veins, 257, 318 Brachytherapy, 257, 286, 308 Bradycardia, 17, 30, 33, 47, 88, 92, 107, 144, 146, 153, 161, 162, 165, 215, 257 Bradykinin, 257, 296 Brain Stem, 257, 299 Branch, 14, 30, 127, 161, 216, 243 Breakdown, 257, 268, 269, 278 Breeding, 33, 257 Broad-spectrum, 257, 260 Bronchi, 257, 274, 287, 319, 321 Bronchial, 257, 319 Bronchitis, 257, 262 Bronchoconstriction, 9, 257 Bronchodilator, 257, 276, 287 Bronchopulmonary, 9, 257 Bronchus, 257 Buffers, 254, 257, 316 Bullous, 258, 268 Bundle-Branch Block, 91, 258 Bupivacaine, 258, 288 Burns, 28, 258 Burns, Electric, 258 Bypass, 57, 220, 258, 294 C Caffeine, 156, 157, 185, 216, 258

Calcium, 13, 20, 25, 26, 27, 36, 40, 51, 53, 54 Calcium channel blocker, 258, 324 Calcium Channels, 41, 258, 299 Capillary, 46, 257, 258, 324 Carbohydrate, 5, 258, 279 Carbon Dioxide, 62, 258, 259, 278, 283, 301, 311, 324 Carcinogen, 258, 292, 322 Carcinogenic, 258, 285, 297, 305, 317 Carcinoma, 7, 105, 219, 258 Cardiac arrest, 27, 34, 35, 55, 66, 79, 141, 157, 173, 259, 318 Cardiac catheterization, 259, 309 Cardiac Glycosides, 13, 259 Cardiac Output, 17, 42, 44, 46, 143, 149, 159, 161, 162, 165, 176, 255, 259, 284, 317 Cardiological, 145, 259 Cardiomyopathy, 21, 22, 36, 40, 43, 44, 55, 71, 76, 80, 89, 91, 102, 106, 165, 194, 208, 259 Cardiomyopathy, Hypertrophic, 165, 259 Cardiopulmonary, 9, 34, 58, 259 Cardioselective, 259, 305 Cardiotocography, 234, 259 Cardiotonic, 259, 269, 270 Cardiovascular Abnormalities, 59, 259 Cardiovascular disease, 6, 15, 37, 53, 60, 181, 259 Cardiovascular Physiology, 59, 259 Cardiovascular System, 23, 138, 254, 259 Cardioversion, 51, 141, 146, 151, 157, 159, 170, 173, 174, 180, 181, 215, 223 Carotid Body, 9, 259, 261 Carotid Sinus, 123, 125, 127, 128, 259, 304 Carrier Proteins, 260, 308 Case report, 73, 74, 85, 102, 106, 260, 263 Case series, 75, 260, 263 Catecholamine, 15, 32, 68, 87, 184, 260, 270, 301 Catheter Ablation, 11, 24, 41, 49, 51, 56, 66, 122, 139, 187, 191, 215 Catheterization, 44, 49, 260, 286, 294 Catheters, 41, 44, 103, 160, 284, 286 Cations, 260, 286 Causal, 260, 281, 311 Cause of Death, 28, 173, 260 Cefotaxime, 4, 260 Cell Death, 26, 43, 260, 275, 278 Cell Differentiation, 260, 314 Cell Division, 208, 254, 260, 275, 280, 291, 292, 302, 305

330

Tachycardia

Cell Fusion, 54, 260 Cell membrane, 156, 185, 255, 258, 260, 268, 272, 278, 301, 303 Cell proliferation, 184, 260, 314 Cell Survival, 260, 280 Central Nervous System, 38, 46, 123, 137, 247, 254, 255, 258, 261, 271, 277, 279, 280, 288, 293, 303, 314, 319 Central Nervous System Infections, 261, 280 Central Venous Pressure, 48, 261 Cerebellar, 253, 261, 310, 322 Cerebellar Diseases, 253, 261, 322 Cerebral, 17, 45, 46, 156, 185 Cerebral Cortex, 253, 261, 275, 276 Cerebrovascular, 9, 45, 255, 259, 261, 319 Cerebrovascular Circulation, 45, 261 Cerebrum, 261, 322 Cervical, 61, 261, 281, 317 Cervix, 261 Cesium, 117, 126, 261 Chaos, 16, 59, 261 Character, 251, 261, 267 CHD, 194, 214, 261, 266, 289 Chemoreceptor, 9, 261 Chemotherapy, 223, 261 Chest Pain, 4, 89, 166, 225, 233, 261 Chest wall, 262, 320 Chin, 262, 291 Cholesterol, 53, 255, 261, 262, 266, 289, 317 Cholesterol Esters, 262, 289 Choline, 247, 262 Cholinergic, 29, 262, 281 Chromosome, 33, 262, 281, 288 Chronic, 5, 7, 8, 17, 21, 22, 23, 27, 31, 35, 37, 42, 44, 45, 61, 116, 117, 123, 125, 154, 156, 172, 181, 185, 208, 219, 220, 226, 227, 229, 234, 235 Chronic Disease, 8, 262 Chronic Fatigue Syndrome, 45, 262 Chronic Obstructive Pulmonary Disease, 117, 125, 226, 235, 262 Chronic renal, 262, 302, 322 Chylomicrons, 262, 289 Circadian, 6, 262 Circadian Rhythm, 6, 262 Circulatory system, 144, 152, 168, 183, 262, 273 Cisplatin, 126, 262 Citrus, 253, 262 Clamp, 12, 25, 52, 58, 262 Clinical study, 48, 263

Clinical trial, 7, 19, 23, 34, 35, 36, 50, 56, 152, 205, 263, 265, 270, 293, 306, 309 Cloning, 256, 263 Coagulation, 188, 189, 256, 263, 281, 320 Codeine, 263, 297 Coenzyme, 253, 263, 296 Cofactor, 263, 306, 320 Cognition, 32, 263, 287 Colectomy, 7, 263 Colitis, 4, 7, 230, 263 Collagen, 11, 189, 250, 255, 263, 302, 305 Collapse, 257, 263, 315 Colon, 4, 189, 208, 263, 285, 287, 291, 305, 314, 322 Colonoscopy, 7, 263 Colostomy, 4, 263 Combination Therapy, 18, 85, 263 Combinatorial, 54, 264 Complement, 264, 290 Complementary and alternative medicine, 121, 131, 264 Complementary medicine, 121, 264 Complete remission, 264, 310 Compliance, 46, 96, 172, 264 Computational Biology, 205, 207, 264 Computer Simulation, 16, 61, 264 Conception, 264, 276, 317 Concomitant, 25, 181, 264 Conduction, 10, 11, 14, 21, 22, 28, 29, 40, 48, 50, 52, 67, 133, 137, 138, 140, 142, 151, 154, 155, 158, 159, 161, 164, 165, 180, 187 Confounding, 15, 17, 265 Congestion, 161, 166, 265, 274 Congestive heart failure, 22, 23, 48, 57, 60, 62, 161, 162, 259, 265 Conjugated, 265, 267, 279 Connective Tissue, 253, 257, 263, 265, 268, 276, 277, 289, 312, 319 Connexins, 13, 265, 278 Consciousness, 35, 169, 173, 250, 265, 267, 270, 307, 311, 319 Constipation, 265, 323 Constriction, 265, 286, 323 Constriction, Pathologic, 265, 323 Consumption, 8, 10, 43, 265, 298 Contractility, 26, 43, 181, 265, 271 Contraindications, ii, 265 Contralateral, 161, 249, 265, 310 Contrast medium, 265, 309 Control group, 265, 304, 309 Conus, 265, 307

331

Conventional therapy, 23, 265 Conventional treatment, 265 Convulsions, 251, 265, 271, 283 Coordination, 161, 162, 265 Coronary Arteriosclerosis, 266, 294 Coronary Artery Bypass, 100, 220, 266 Coronary Circulation, 8, 43, 251, 266 Coronary Disease, 10, 266 Coronary heart disease, 259, 261, 266 Coronary Thrombosis, 266, 292, 294 Coronary Vessels, 266 Corpus, 266, 300, 305, 314 Corpus Luteum, 266, 305 Cortex, 266, 310 Cortical, 156, 185, 266, 275, 313, 319 Corticosteroids, 7, 266 Cranial, 266, 280, 295, 299, 300, 323 Craniocerebral Trauma, 255, 266, 280, 319 Creatinine, 4, 266, 322 Criterion, 97, 148, 178, 266 Curative, 35, 139, 266, 320 Cyclic, 87, 121, 248, 258, 266, 280, 296, 303, 305, 320 Cyst, 90, 102, 266 Cytochrome, 43, 266 Cytokines, 15, 22, 267 Cytoplasm, 255, 260, 267, 273, 275, 279, 294, 296, 312 Cytoskeleton, 52, 267 Cytotoxic, 267, 309, 314 Cytotoxicity, 262, 267 D Data Collection, 23, 267 Databases, Bibliographic, 205, 267 Decidua, 267, 301 Decompression, 267, 270 Defibrillation, 16, 20, 27, 55, 141, 146, 149, 151, 157, 159, 163, 165, 166, 169, 170, 171, 173, 176, 177, 180, 215, 267 Degenerative, 265, 267, 272, 297 Dehydration, 3, 7, 224, 267 Deletion, 182, 267 Delirium, 224, 231, 267 Delivery of Health Care, 268, 280 Delusions, 268, 307 Dendrites, 268, 295 Density, 28, 36, 42, 62, 256, 268, 289, 297, 316 Dentition, 3, 268 Depersonalization, 268, 299, 313 Depolarization, 12, 63, 136, 140, 142, 151, 159, 161, 163, 171, 173, 180, 268, 269, 314

Depressive Disorder, 236, 268 Derealization, 268, 299 Dermatitis, 172, 268 Dermatitis Herpetiformis, 172, 268 Dermatosis, 172, 268 Dermis, 251, 268 Detergents, 268, 277 Diabetes Mellitus, 3, 230, 234, 268, 279, 281 Diabetic Ketoacidosis, 3, 268 Diagnostic Errors, 29, 269 Diagnostic procedure, 135, 195, 269 Diaphoresis, 18, 269 Diarrhea, 4, 18, 232, 250, 269, 285 Diarrhoea, 269, 283 Diastole, 143, 168, 269 Diastolic, 6, 12, 22, 58, 69, 77, 144, 168, 269, 282 Diffusion, 63, 255, 269 Digestion, 8, 249, 255, 257, 269, 286, 289, 300, 317 Digestive tract, 254, 269, 315 Digitalis, 74, 122, 123, 128, 259, 269, 297 Dihydroprogesterone, 46, 269 Dilatation, 22, 250, 251, 269, 304, 323 Dilatation, Pathologic, 269, 323 Dilated cardiomyopathy, 21, 44, 69, 88, 95, 166, 269 Dilation, 166, 257, 269, 323 Diltiazem, 80, 118, 194, 269 Dilution, 18, 269, 274, 302 Direct, iii, 6, 9, 43, 49, 51, 57, 168, 184, 189 Discrete, 50, 154, 183, 269, 319 Discrimination, 71, 80, 143, 152, 155, 158, 170, 186, 269 Disinfectant, 269, 274 Disopyramide, 116, 269 Disorientation, 267, 270 Dissection, 20, 51, 189, 270 Dissociation, 101, 248, 270, 286, 319 Dissociative Disorders, 270 Distal, 180, 260, 266, 270, 272, 306 Diuresis, 258, 270, 319 Diverticulum, 232, 270 Diving, 88, 270 Dizziness, 9, 35, 172, 270, 299 Dobutamine, 44, 270 Docosahexaenoic Acids, 10, 270 Dopamine, 156, 185, 270, 292, 296, 301 Dorsal, 270, 295, 303 Double-blind, 45, 270 Drive, ii, vi, 15, 38, 94, 115, 270

332

Tachycardia

Drug Interactions, 11, 198, 270 Drug Tolerance, 271, 320 Duct, 250, 260, 271, 312 Duodenum, 255, 271, 273, 300, 317 Dyes, 22, 29, 51, 250, 255, 271, 296 Dysphoric, 268, 271 Dysplasia, 7, 66, 85, 209, 271 Dyspnea, 9, 95, 166, 271, 299 Dystrophin, 181, 182, 271 Dystrophy, 38, 71, 181, 182, 208, 271 E Eating Disorders, 228, 271 Echocardiography, 64, 102, 110, 271 Eclampsia, 43, 271 Ectoderm, 271, 295 Ectopic, 76, 93, 94, 95, 103, 107, 110, 117, 126, 154, 168, 178, 271 Edema, 17, 251, 271, 294, 304, 322 Effector, 14, 247, 264, 271 Efferent, 29, 46, 271 Efficacy, 24, 34, 45, 56, 66, 92, 108, 126, 172, 271 Ejection fraction, 6, 22, 23, 271 Elastin, 263, 271 Elastomers, 165, 271 Elective, 272 Electric Conductivity, 28, 272 Electric shock, 64, 151, 159, 169, 180, 267, 272 Electrocardiogram, 14, 49, 60, 139, 145, 148, 151, 154, 157, 158, 168, 180, 227 Electrocardiography, 49, 68, 85, 111, 192, 272 Electrocoagulation, 263, 272 Electrode, 27, 44, 138, 139, 160, 171, 180, 272 Electrolyte, 4, 5, 138, 268, 272, 303, 315, 322 Electromagnetic Fields, 61, 272 Electrophysiological, 14, 21, 35, 39, 40, 42, 51, 52, 61, 62, 64, 71, 76, 82, 92, 191, 253, 272, 324 Electroporation, 27, 272 Emboli, 25, 51, 272 Embolization, 25, 51, 272 Embolus, 272, 284 Embryo, 256, 260, 271, 272, 276, 284, 304 Embryology, 272, 276 Emergency Medical Services, 55, 272 Emphysema, 262, 272 Encephalomalacia, 124, 272 Endemic, 272, 290, 316

Endocardium, 27, 35, 81, 138, 187, 273 Endocrine System, 273 Endocrinology, 31, 59, 273 Endogenous, 5, 46, 270, 273 Endometrium, 267, 273, 291 Endorphins, 273, 296 Endoscope, 273 Endoscopic, 111, 189, 233, 263, 273, 314 Endothelial cell, 256, 273, 320 Endothelium, 273, 296 Endothelium-derived, 273, 296 Endotoxin, 28, 273 End-stage renal, 262, 273, 302 Energy balance, 9, 273 Energy Intake, 8, 273 Enkephalins, 273, 296 Environmental Exposure, 33, 273, 297 Environmental Health, 47, 204, 206, 273 Enzymatic, 250, 258, 264, 273 Enzyme, 247, 248, 263, 271, 273, 278, 280, 294, 306, 314, 318, 320, 325 Eosinophils, 249, 273, 279, 288 Epidermis, 268, 274, 308 Epinephrine, 117, 181, 248, 270, 274, 287, 296, 322 Epizootic, 225, 274 Erection, 274, 304 ERV, 206, 274, 275 Erythema, 5, 274, 323 Erythema Nodosum, 5, 274 Erythrocyte Indices, 256, 274 Erythrocyte Volume, 256, 274 Erythrocytes, 250, 256, 257, 274, 281, 310 Esophageal, 189, 274, 313 Esophageal Varices, 274, 313 Esophagus, 269, 274, 300, 301, 317 Essential Tremor, 209, 274 Ethanol, 26, 274 Ethanolamine, 274, 292 Ether, 36, 275 Etoposide, 126, 275 Evoke, 275, 317 Excitability, 54, 275, 294, 295, 308 Excitation, 18, 26, 40, 52, 62, 127, 151, 152, 161, 173, 253, 261, 275, 296 Excitatory, 46, 151, 158, 161, 180, 275, 279 Exercise Test, 219, 275 Exercise Tolerance, 48, 275 Exhaustion, 251, 275, 290 Exogenous, 46, 256, 273, 275, 322 Exons, 55, 275 Expiratory, 274, 275

333

Expiratory Reserve Volume, 274, 275 External-beam radiation, 275, 308 Extracellular, 11, 13, 16, 21, 157, 186, 250, 265, 275, 292, 315 Extracellular Matrix, 21, 265, 275 Extracellular Space, 275 Extrapyramidal, 270, 276 Extrasystole, 144, 276 Extremity, 221, 261, 276, 287, 299, 313 Exudate, 276, 297 F Facial, 249, 276, 290, 299, 315 Facial Paralysis, 249, 276 Family Planning, 205, 276 Fat, 59, 248, 252, 257, 261, 266, 272, 276, 287, 288, 297, 303, 312, 315, 322 Fatigue, 5, 17, 45, 159, 165, 262, 276, 280 Fatty acids, 10, 43, 52, 269, 270, 276, 305, 315 Febrile, 91, 276, 290 Feces, 265, 276, 317 Fenoterol, 107, 276 Fetal Blood, 276, 290 Fetal Development, 182, 276 Fetal Heart, 50, 228, 259, 276 Fetal Monitoring, 234, 276 Fetus, 63, 276, 301, 304, 323 Fibroma, 87, 276 Fibrosis, 10, 209, 276, 312, 313 Filtration, 17, 46, 98, 277 Fish Oils, 218, 270, 277 Flatus, 277, 278 Flecainide, 85, 93, 100, 277 Fluorescence, 12, 14, 277 Flutter, 11, 51, 57, 146, 154, 163, 171, 175, 181, 184, 188, 189, 218, 277 Fold, 55, 277, 291 Foramen, 262, 277, 290, 300 Forearm, 256, 277 Free Radicals, 252, 270, 277, 294 Friction, 165, 249, 277 G Gallbladder, 247, 255, 277 Gamma Rays, 277, 308, 309 Ganglia, 29, 42, 61, 247, 255, 277, 295, 299, 300, 317, 318 Ganglion, 26, 42, 277, 295, 316 Ganglionic Blockers, 277, 281 Gap Junctions, 21, 40, 52, 265, 277 Gas, 62, 258, 269, 274, 277, 278, 282, 285, 296, 311, 318, 324 Gas exchange, 63, 278, 311, 324

Gastric, 254, 278, 300, 313 Gastrin, 278, 282 Gastrointestinal, 189, 232, 233, 252, 257, 274, 278, 281, 283, 288, 290, 295, 314, 315, 318 Gastrointestinal tract, 252, 274, 278, 281, 288, 314 Gene Expression, 32, 43, 54, 55, 209, 278 Gene Therapy, 26, 278 Generator, 146, 149, 176, 179, 278 Genetics, 39, 55, 87, 278, 293 Genital, 254, 278 Genomics, 32, 278 Genotype, 32, 278, 301 Gestation, 32, 85, 278, 301, 304 Giant Cells, 278, 312 Giardiasis, 278, 292 Gland, 248, 278, 289, 298, 299, 306, 313, 317, 320 Glucose, 5, 6, 15, 33, 43, 193, 208, 253, 256, 268, 279, 281, 283, 285, 312 Glucose Intolerance, 268, 279 Glucose tolerance, 15, 279 Glucose Tolerance Test, 279 Glutamic Acid, 279, 296, 305 Glycine, 250, 279, 296 Glycoproteins, 258, 279, 286, 291, 303 Glycoside, 279, 297, 312 Gonadal, 279, 317 Governing Board, 279, 303 Grade, 22, 42, 279 Graft, 220, 221, 279, 294 Grafting, 100, 266, 279, 284 Gram-negative, 28, 279, 312 Granulocytes, 249, 279, 314, 325 Groin, 279, 285 Growth, 7, 18, 51, 58, 182, 184, 208, 221 Growth factors, 58, 280 Guanylate Cyclase, 280, 296 H Habitual, 9, 77, 261, 280 Haematoma, 83, 280 Half-Life, 19, 156, 185, 280 Hamartoma, 95, 280 Haplotypes, 33, 280 Haptens, 248, 280, 308 Headache, 172, 258, 280, 283 Headache Disorders, 280 Health Care Costs, 97, 280 Health Expenditures, 280 Heart attack, 160, 187, 259, 280 Heart Transplantation, 43, 280

334

Tachycardia

Heartbeat, 3, 4, 7, 138, 154, 159, 164, 165, 171, 187, 215, 218, 253, 280, 318, 324 Hematocrit, 256, 274, 280 Heme, 5, 266, 281, 303 Hemiplegia, 249, 281 Hemodynamics, 48, 51, 59, 174, 281 Hemoglobin, 5, 250, 256, 274, 281, 303 Hemoglobinopathies, 278, 281 Hemoglobinuria, 208, 281 Hemolysis, 172, 281 Hemorrhage, 5, 7, 266, 272, 280, 281, 294, 317 Hemorrhoids, 4, 281, 313 Hemostasis, 281, 314 Hepatic, 5, 268, 279, 281, 303 Hereditary, 281, 302, 311 Heredity, 278, 281 Herpetiformis, 172, 268, 281 Heterogeneity, 20, 52, 88, 89, 248, 281 Heterozygote, 14, 281 Hexamethonium, 29, 281 Homeostasis, 23, 47, 282, 299, 315 Homologous, 249, 265, 278, 281, 282, 318 Homozygote, 14, 282 Hormonal, 6, 58, 253, 282 Hormone, 26, 32, 262, 266, 274, 278, 282, 285, 305, 312, 314, 320 Hybrid, 282 Hybridization, 42, 260, 282, 293 Hybridomas, 272, 282 Hydrogen, 247, 255, 257, 258, 282, 288, 293, 296, 297, 298, 300, 306 Hydrolysis, 247, 256, 262, 282, 301 Hydrophilic, 165, 268, 282 Hydrophobic, 268, 282, 289 Hydroxylysine, 263, 282 Hydroxyproline, 250, 263, 282 Hyperoxaluria, 109, 282 Hyperphagia, 18, 282 Hypersensitivity, 6, 282, 288, 312 Hypertension, 5, 15, 18, 32, 45, 47, 59, 86, 109, 137, 156, 185, 208, 225, 235, 259, 280, 281, 282, 304, 305, 322 Hyperthyroidism, 53, 282, 305 Hypertrophic cardiomyopathy, 84, 101, 165, 166, 282 Hypertrophy, 22, 25, 57, 59, 259, 282 Hypesthesia, 283, 295 Hypocapnia, 45, 283 Hypoglycaemia, 268, 283 Hypokalaemia, 124, 283

Hypotension, 5, 6, 8, 17, 18, 45, 80, 139, 181, 265, 277, 283, 292 Hypothalamus, 254, 283 Hypothermia, 34, 283 Hypotonic Solutions, 5, 283 Hypovolemia, 17, 283 Hypoxemia, 226, 283 Hypoxia, 34, 268, 283, 319 Hypoxic, 283, 292 I Iatrogenic, 19, 56, 74, 283 Idiopathic, 39, 69, 71, 72, 77, 78, 81, 82, 87, 91, 93, 94, 95, 96, 99, 103, 108, 112, 139, 182, 283, 312 Immune response, 251, 280, 283, 284, 290, 318, 324 Immune system, 255, 283, 284, 288, 289, 323, 325 Immunization, 283, 304 Immunodeficiency, 208, 283 Immunogenic, 283, 308 Immunoglobulin, 228, 251, 275, 284, 293 Immunohistochemistry, 27, 284 Immunology, 21, 234, 248, 284 Immunosuppressive, 7, 284 Immunosuppressive therapy, 7, 284 Impairment, 15, 73, 253, 267, 284, 288, 291, 307 Implant radiation, 284, 286, 308 Implantation, 70, 147, 221, 264, 284 In situ, 12, 173, 284 In vitro, 12, 16, 25, 28, 36, 39, 43, 59, 260, 278, 284, 320 In vivo, 12, 16, 25, 26, 28, 36, 40, 53, 58, 59, 260, 278, 284, 320 Incidental, 107, 284 Incision, 263, 284, 286, 287, 320 Incisional, 74, 154, 284 Incubation, 284, 288 Incubation period, 284, 288 Indicative, 140, 141, 148, 191, 284, 299, 323 Indocyanine Green, 18, 284 Induction, 12, 14, 27, 42, 60, 61, 90, 94, 117, 177, 277, 284 Infancy, 128, 284 Infarction, 4, 6, 22, 23, 25, 27, 42, 49, 50, 52, 56, 64, 125, 184, 186, 187, 219, 220, 229, 230, 235 Infection, 3, 28, 231, 250, 255, 268, 274, 278, 283, 284, 285, 288, 289, 296, 312, 317, 322, 323, 325 Infectious Diarrhea, 232, 285

335

Infertility, 214, 285 Inflammation, 156, 185 Inflammatory bowel disease, 4, 7, 285 Informed Consent, 35, 285 Infusion, 42, 44, 87, 146, 193, 285, 294, 313 Ingestion, 279, 282, 285, 302 Inguinal, 189, 285 Inhalation, 107, 285, 302 Initiation, 12, 13, 15, 21, 25, 28, 30, 50, 67, 92, 97, 111, 178, 285 Inlay, 285, 311 Innervation, 6, 14, 29, 137, 285, 300, 313 Inorganic, 262, 285, 293 Inotropic, 4, 43, 67, 270, 285 Insight, 9, 13, 15, 16, 41, 60, 285 Insomnia, 18, 172, 285 Insufflation, 63, 285 Insulin, 9, 33, 43, 193, 268, 279, 285, 287, 322 Insulin-dependent diabetes mellitus, 285 Intensive Care, 34, 285 Intensive Care Units, 34, 285 Intermittent, 285, 289, 300 Internal Medicine, 31, 38, 48, 57, 83, 116, 117, 118, 124, 273, 286 Internal radiation, 286, 308 Interstitial, 10, 46, 257, 275, 283, 286, 310 Intestinal, 184, 279, 286, 290 Intestine, 257, 286, 287 Intoxication, 122, 268, 286, 325 Intracellular, 12, 13, 26, 27, 29, 36, 51, 53, 57, 156, 185 Intraindividual, 116, 286 Intramuscular, 286, 299 Intravascular, 180, 189, 227, 286 Intravenous, 5, 9, 28, 93, 116, 123, 124, 228, 285, 286, 299 Intrinsic, 26, 48, 61, 146, 150, 161, 171, 248, 255, 286 Intubation, 260, 286 Invasive, 19, 23, 41, 44, 49, 56, 60, 61, 106, 181, 189, 286, 289, 309 Involuntary, 255, 274, 276, 286, 294, 310, 323, 325 Ion Channels, 14, 20, 33, 41, 58, 183, 286 Ion Exchange, 286 Ionization, 286 Ionizing, 249, 273, 286, 309 Ions, 13, 57, 247, 255, 257, 258, 270, 272, 282, 286, 303, 312 Iontophoresis, 11, 286 Ipsilateral, 127, 249, 286, 310

Ischemia, 4, 6, 9, 17, 19, 21, 38, 41, 50, 56, 63, 112, 125, 156, 166, 174, 178, 185, 253, 286, 294, 310 Isoproterenol, 79, 87, 116, 287 J Joint, 234, 253, 272, 287, 297, 318 K Kb, 204, 287 Ketoacidosis, 3, 287 Ketone Bodies, 269, 287 Ketosis, 269, 287 Kidney Disease, 204, 209, 229, 287 Kinetic, 25, 286, 287 L Labile, 25, 264, 287 Language Development, 182, 287 Laparoscopy, 63, 287 Laparotomy, 4, 287 Large Intestine, 269, 286, 287, 310, 315 Larynx, 287, 321, 323 Latency, 9, 287 Latent, 12, 95, 163, 287, 304 Leg Ulcer, 227, 287 Lentivirus, 42, 288 Leprosy, 172, 288 Lesion, 4, 28, 35, 138, 189, 249, 266, 288, 289, 293, 312 Lethal, 14, 20, 40, 56, 179, 217, 254, 288 Leukemia, 208, 278, 288 Leukocytes, 255, 256, 257, 267, 273, 279, 288, 296 Leukocytosis, 4, 5, 288 Leukotrienes, 252, 288 Levofloxacin, 96, 104, 288 Library Services, 242, 288 Lidocaine, 9, 288, 292 Life Expectancy, 174, 288 Ligament, 288, 306 Ligands, 54, 288 Ligation, 4, 288 Liminal, 38, 288 Linkage, 33, 288 Linkage Disequilibrium, 33, 288 Lipid, 33, 54, 252, 262, 285, 288, 289, 298 Lipid Peroxidation, 288, 298 Lipopolysaccharide, 279, 289 Lipoprotein, 53, 279, 289 Liver, 189, 247, 252, 255, 274, 276, 277, 279, 281, 284, 289, 312 Localization, 19, 24, 66, 71, 154, 168, 284, 288, 289

336

Tachycardia

Localized, 4, 12, 247, 251, 271, 280, 281, 284, 289, 293, 302, 313, 323 Locomotion, 289, 302 Locomotor, 182, 289 Long-Term Care, 231, 289 Loop, 80, 90, 127, 168, 187, 289 Low-density lipoprotein, 289 Lumen, 44, 165, 289 Lymph, 254, 261, 262, 273, 289, 312 Lymph node, 254, 261, 289, 312 Lymphatic, 273, 284, 289, 316 Lymphocyte, 252, 289, 290, 291 Lymphoid, 251, 266, 289 Lymphoma, 208, 289 M Magnetic Resonance Imaging, 19, 41, 289 Maintenance therapy, 7, 289 Major Histocompatibility Complex, 280, 290 Malabsorption, 208, 290 Malaise, 3, 290 Malaria, 172, 290 Malaria, Falciparum, 290 Malaria, Vivax, 290 Malformation, 280, 290 Malignant, 56, 86, 153, 194, 208, 290, 295, 309, 312 Malnutrition, 5, 253, 290, 293 Mammary, 189, 266, 290 Manic, 256, 290, 307 Manic-depressive psychosis, 290, 307 Manifest, 4, 7, 47, 61, 281, 290 Maternal-Fetal Exchange, 63, 290 Meatus, 290, 323 Mechanical ventilation, 19, 117, 125, 290 Medial, 11, 290 Mediate, 157, 270, 290 Mediator, 8, 290, 314 Medical Records, 21, 33, 34, 291 MEDLINE, 205, 207, 209, 291 Megacolon, 5, 291 Meiosis, 291, 318 Melanin, 291, 301, 322 Melanocytes, 291 Melanoma, 208, 291 Membrane Glycoproteins, 291 Memory, 23, 25, 142, 169, 172, 251, 267, 291 Meninges, 261, 266, 291 Menopause, 291, 305 Menstrual Cycle, 31, 291, 305 Menstruation, 267, 291

Mental, iv, 7, 26, 182, 204, 206, 210, 261, 262, 263, 267, 270, 276, 291, 295, 304, 307, 312, 313, 322 Mental Disorders, 291, 304, 307 Mental Health, iv, 7, 204, 206, 291, 304, 307 Mental Processes, 270, 291, 307 Mercaptopurine, 7, 291 Mesenteric, 45, 291 Mesentery, 291, 300 Metabolite, 46, 256, 291 Metastasis, 65, 291 Metoclopramide, 127, 292 Metronidazole, 4, 292 Mexiletine, 192, 292 MI, 25, 42, 103, 194, 245, 292 Microbe, 292, 321 Microbiology, 248, 254, 292 Microorganism, 263, 292, 325 Microscopy, 12, 58, 62, 255, 292 Midodrine, 18, 292 Migration, 26, 111, 292 Mitogen-Activated Protein Kinase Kinases, 292 Mitogen-Activated Protein Kinases, 58, 292 Mitosis, 252, 292 Mitotic, 275, 292 Mobilization, 5, 292 Modeling, 26, 55, 60, 292 Modification, 42, 66, 98, 99, 125, 139, 250, 293, 308 Modulator, 46, 293 Molecular, 15, 20, 21, 27, 36, 39, 40, 52, 54, 55, 59, 205, 207, 256, 264, 272, 293, 309, 312, 316, 321 Molecular Probes, 272, 293 Monitor, 11, 35, 49, 51, 55, 141, 146, 266, 293, 296 Monoclonal, 65, 282, 293, 308 Monogenic, 26, 33, 293 Morphine, 19, 263, 293, 294, 297 Morphology, 11, 80, 81, 106, 123, 145, 152, 154, 155, 168, 186, 293 Motility, 293, 314 Motion Sickness, 293, 295 Mouth Ulcer, 5, 293 Mucinous, 277, 293 Mucus, 293, 322 Multicenter Studies, 51, 293 Multicenter study, 293 Muscle Contraction, 271, 293, 312

337

Muscle Fibers, 161, 182, 253, 293, 294, 315, 322 Muscular Atrophy, 208, 293 Muscular Dystrophies, 271, 294 Musculature, 86, 294 Mydriatic, 269, 294 Myocardial Contraction, 136, 294 Myocardial Ischemia, 6, 21, 56, 125, 174, 178, 251, 266, 294 Myocardial Reperfusion, 294, 311 Myocardial Reperfusion Injury, 294, 311 Myofibrils, 271, 294 Myosin, 293, 294, 322 Myotonic Dystrophy, 208, 294 N Narcolepsy, 232, 294 Narcosis, 294 Narcotic, 18, 293, 294 Nausea, 172, 223, 251, 287, 294, 299, 322 Need, 3, 4, 6, 63, 140, 153, 172, 192, 198, 199, 237, 248, 262, 295, 320 Neonatal, 14, 18, 21, 51, 67, 92, 100, 102, 112, 222, 224, 225, 227, 228, 295 Neonatal Abstinence Syndrome, 18, 295 Neoplasia, 208, 295 Neoplasm, 280, 295, 312, 322 Neoplastic, 282, 289, 295 Nephron, 33, 295 Nephropathy, 287, 295 Nerve Growth Factor, 42, 295 Nervous System, 26, 37, 38, 46, 123, 137, 178, 182, 209 Nervousness, 172, 295 Neural, 9, 15, 26, 30, 31, 38, 42, 47, 175, 248, 250, 277, 295 Neural Crest, 26, 295 Neural Pathways, 9, 30, 295 Neuritis, 172, 295 Neurogenic, 38, 45, 295, 323 Neurologic, 18, 34, 295 Neuromuscular, 181, 182, 247, 276, 283, 295, 322 Neuromuscular Junction, 247, 295 Neuronal, 30, 46, 258, 294, 295 Neurons, 29, 46, 156, 185, 268, 275, 277, 295, 318 Neuropathy, 6, 38, 254, 296 Neurophysiology, 268, 296 Neurotransmitter, 32, 247, 248, 250, 257, 270, 279, 286, 296, 314, 317 Neutrons, 249, 296, 308 Neutrophils, 249, 279, 288, 296

Niacinamide, 296 Nicorandil, 117, 296 Nitric Oxide, 43, 52, 63, 296 Norepinephrine, 6, 13, 55, 84, 101, 248, 270, 296 Nuclear, 53, 232, 249, 255, 277, 296 Nuclei, 249, 250, 275, 276, 278, 289, 292, 296, 299, 302, 306 Nucleic acid, 282, 296 Nucleic Acid Hybridization, 282, 297 Nucleus, 255, 266, 267, 273, 277, 291, 296, 297, 305, 306, 315, 317, 319 O Odour, 252, 297, 322 Oncogene, 208, 297 Oncogenic, 288, 297 Opacity, 268, 297 Open Reading Frames, 288, 297 Opiate, 293, 297 Opium, 19, 293, 297, 299 Oral Health, 4, 297 Orderly, 138, 297 Organ Culture, 297, 320 Orthostatic, 6, 17, 31, 37, 45, 55, 58, 74, 84, 86, 87, 96, 101, 102, 297 Osmolarity, 57, 297 Osmoles, 297 Osmotic, 283, 297, 314 Osteoarthritis, 226, 297 Ouabain, 16, 297 Outpatient, 4, 23, 34, 297 Overexpress, 22, 297 Overweight, 60, 119, 297 Ovum, 266, 267, 278, 298, 305, 325 Oxalate, 282, 298 Oxidation, 252, 256, 266, 269, 288, 298 Oxidative Stress, 43, 298 Oxygen Consumption, 8, 43, 275, 298, 311 Oxygenation, 283, 298 P Pacer, 169, 179, 298 Paediatric, 85, 103, 298 Palliative, 298, 320 Pallor, 5, 298 Palsy, 249, 298 Pancreas, 247, 285, 298 Pancreatic, 208, 298 Pancreatic cancer, 208, 298 Pancreatitis, 28, 130, 221, 298 Panic, 229, 298 Panic Disorder, 229, 298 Papaverine, 297, 299

338

Tachycardia

Paralysis, 276, 283, 299 Parasite, 5, 299, 322 Parasympathetic Nervous System, 24, 299 Parenteral, 5, 273, 299 Paresis, 276, 281, 295, 299 Paresthesias, 295, 299 Parietal, 299, 300 Parotid, 299, 312 Paroxysmal, 61, 116, 118, 124, 125, 126, 127, 128, 133, 139, 156, 185, 208 Partial remission, 299, 310 Parturition, 43, 299 Patch, 12, 14, 58, 265, 299 Pathogenesis, 6, 21, 22, 39, 45, 299 Pathologic, 150, 247, 255, 266, 282, 299, 307 Pathologies, 10, 26, 62, 299 Pathophysiology, 6, 28, 37, 43, 45, 58, 192, 300 Pelvic, 4, 18, 300, 306 Pelvis, 247, 300, 323 Penis, 300, 304 Peptic, 300, 313 Peptic Ulcer, 300, 313 Peptic Ulcer Hemorrhage, 300, 313 Peptide, 26, 47, 250, 300, 306 Percutaneous, 69, 139, 300, 301 Perforation, 5, 277, 300 Perfusion, 19, 45, 62, 166, 283, 300 Perioperative, 220, 300 Peripheral blood, 77, 300 Peripheral Nervous System, 273, 281, 296, 298, 300, 317 Peritoneal, 62, 230, 300 Peritoneal Cavity, 62, 300 Peritoneal Dialysis, 230, 300 Peritoneum, 63, 291, 300, 311 Peroneal Nerve, 38, 58, 300, 313 Perspiration, 269, 300 PH, 47, 62, 300 Pharmacodynamics, 19, 109, 301 Pharmacokinetic, 301 Pharmacologic, 31, 118, 126, 223, 250, 280, 301, 321, 323 Pharmacotherapy, 40, 86, 100, 301 Pharynx, 301, 323 Phenotype, 21, 32, 40, 182, 301 Phenyl, 269, 301 Phenylalanine, 301, 322 Phonophoresis, 286, 301 Phospholipases, 301, 314 Phospholipids, 276, 289, 301, 306 Phosphorus, 258, 301

Phosphorylation, 58, 292, 301, 306 Photocoagulation, 263, 301 Physical Examination, 4, 301 Physiologic, 19, 62, 143, 249, 276, 280, 291, 301, 305, 309, 319, 322 Physiology, 8, 11, 12, 15, 20, 29, 42, 43, 52, 57, 59, 60, 116 Pilot study, 29, 301 Placenta, 43, 276, 301, 305 Plants, 249, 253, 255, 257, 258, 259, 262, 269, 279, 293, 296, 297, 302, 303, 312, 321, 322 Plaque, 11, 302 Plasma, 5, 8, 10, 28, 33, 45, 46, 53, 63 Plasma cells, 251, 302 Plasma Volume, 45, 46, 256, 302 Plasmids, 272, 302 Platelet Activation, 302, 314 Platelet Aggregation, 296, 302, 320 Platelets, 296, 302, 320 Platinum, 165, 166, 262, 289, 302 Pleomorphic, 125, 302 Plethysmography, 18, 46, 302 Pneumonia, 172, 265, 302 Podophyllotoxin, 275, 302 Poisoning, 116, 122, 268, 286, 295, 302, 313 Polycystic, 209, 302 Polymers, 302, 306, 317 Polymorphic, 33, 50, 61, 68, 71, 73, 75, 83, 84, 96, 103, 104, 107, 117, 126, 208, 303 Polyunsaturated fat, 10, 303, 320 Pons, 249, 257, 276, 303 Porphyria, 5, 303 Porphyrins, 303 Port, 103, 189, 303 Port-a-cath, 303 Post partum, 43, 303 Posterior, 252, 253, 270, 298, 303 Postoperative, 4, 51, 57, 100, 103, 110, 117, 126, 223, 303 Postoperative Period, 4, 303 Postprandial, 8, 303 Postsynaptic, 303, 314 Post-translational, 40, 303 Postural, 17, 31, 37, 45, 46, 55, 74, 77, 87, 88, 96, 98, 101, 102, 104, 194, 216, 303 Potassium, 11, 20, 25, 52, 283, 296, 303, 308, 315 Potassium Channels, 25, 52, 303 Potentiation, 41, 303, 314 Practice Guidelines, 206, 219, 220, 221, 224, 230, 231, 303

339

Preclinical, 44, 304 Precordial, 113, 304 Precursor, 252, 262, 270, 271, 273, 296, 301, 304, 322 Predisposition, 33, 304 Pre-Eclampsia, 43, 304 Pre-eclamptic, 271, 304 Pre-Excitation Syndromes, 127, 304 Prenatal, 182, 272, 304 Prenatal Diagnosis, 182, 304 Preoperative, 51, 304 Pressoreceptors, 254, 304 Presynaptic, 296, 304 Prevalence, 61, 304 Priapism, 234, 304 Primary endpoint, 23, 51, 304 Primary Prevention, 56, 304 Probe, 54, 64, 139, 188, 189, 304 Procaine, 288, 304 Proctitis, 7, 304 Proctosigmoiditis, 7, 304 Proctosigmoidoscopy, 5, 305 Progesterone, 46, 269, 305, 317 Progression, 6, 150, 251, 305 Progressive, 60, 86, 166, 260, 262, 271, 279, 294, 297, 302, 305, 310, 322 Projection, 296, 305, 310 Proline, 263, 282, 305 Promoter, 54, 305 Prone, 49, 66, 174, 305 Prone Position, 174, 305 Prophase, 305, 318 Prophylaxis, 99, 174, 181, 305, 311 Propofol, 108, 305 Propranolol, 86, 305 Prospective Studies, 6, 305 Prospective study, 101, 305 Prostaglandin, 116, 305, 320 Prostaglandins A, 305, 306 Prostate, 189, 208, 306 Prosthesis, 136, 141, 306 Protease, 263, 306 Protein C, 182, 250, 252, 254, 289, 306, 316, 322 Protein Kinase C, 292, 306 Protein Kinases, 58, 292, 306 Protein S, 26, 209, 256, 306 Proteins, 13, 15, 40, 42, 53, 62, 250, 252, 256, 260, 263, 264, 265, 267, 271, 272, 278, 282, 293, 294, 300, 302, 303, 306, 309, 314, 316

Protein-Serine-Threonine Kinases, 292, 306 Proteinuria, 304, 306 Protocol, 18, 19, 28, 51, 121, 160, 179, 306 Protons, 249, 282, 286, 306, 308 Protozoan, 261, 278, 290, 306, 322 Proximal, 11, 270, 304, 306, 313 Pruritic, 268, 306 Psoriasis, 307, 311 Psychiatric, 46, 231, 291, 307 Psychiatry, 307, 317, 324 Psychic, 291, 307, 313 Psychoactive, 307, 325 Psychogenic, 307, 323 Psychology, 37, 77, 270, 307 Psychomotor, 267, 307 Psychosis, 172, 307 Public Health, 141, 206, 235, 307 Public Policy, 205, 307 Publishing, 4, 7, 65, 307 Pulmonary Artery, 140, 189, 256, 307, 324 Pulmonary Circulation, 138, 307 Pulmonary congestion, 161, 307 Pulmonary hypertension, 47, 307 Pulmonary Valve, 91, 307 Pulmonary Veins, 61, 82, 152, 154, 188, 189, 307 Pulsation, 277, 307 Pulse, 27, 34, 137, 143, 144, 146, 147, 149, 151, 155, 159, 162, 164, 173, 175, 176, 179, 180, 221 Pupil, 269, 294, 308 Pustular, 172, 281, 308 Q Quality of Life, 11, 22, 23, 48, 57, 182, 308 Quinidine, 116, 117, 124, 308 Quinine, 308 R Race, 138, 249, 292, 308 Racemic, 249, 308 Radiation, 4, 41, 139, 223, 247, 251, 273, 275, 277, 286, 292, 308, 309, 325 Radiation therapy, 223, 247, 275, 286, 308 Radioactive, 280, 282, 284, 286, 293, 296, 297, 308, 309 Radiofrequency ablation, 44, 71, 72, 82, 85, 94, 95, 97, 100, 103, 105, 139, 193, 194, 308 Radiography, 4, 308 Radioimmunoassay, 27, 308 Radiolabeled, 308 Radiological, 300, 308

340

Tachycardia

Radionuclide Imaging, 6, 309 Radionuclide Ventriculography, 232, 309 Radiopharmaceutical, 278, 309 Radiotherapy, 257, 308, 309 Random Allocation, 309 Randomization, 23, 309 Randomized, 10, 19, 23, 34, 45, 51, 56, 99, 101, 121, 271, 309 Randomized clinical trial, 23, 34, 56, 309 Reactivation, 25, 309 Reactive Oxygen Species, 43, 309 Reality Testing, 307, 309 Receptors, Serotonin, 309, 314 Recombinant, 32, 42, 309, 324 Recombination, 278, 310 Rectal, 4, 7, 127, 129, 310 Rectum, 4, 7, 252, 257, 263, 269, 277, 278, 285, 287, 304, 305, 306, 310, 314 Recurrence, 49, 51, 86, 126, 178, 181, 256, 262, 290, 310 Red blood cells, 8, 274, 310, 312 Red Nucleus, 253, 310 Reentry, 50, 51, 57, 64, 67, 70, 71, 77, 82, 86, 89, 92, 139, 187, 310 Refer, 1, 136, 264, 270, 273, 289, 296, 307, 310, 314, 321 Reflective, 138, 310 Reflex, 9, 17, 29, 37, 310 Refraction, 310, 316 Refractory, 70, 85, 104, 106, 137, 143, 147, 151, 159, 165, 180, 184, 193, 272, 310 Regimen, 6, 271, 301, 310, 311 Registries, 50, 310 Regurgitation, 57, 310 Reliability, 157, 310 Remission, 7, 256, 289, 290, 310 Renal failure, 268, 310 Reperfusion, 156, 185, 294, 310 Reperfusion Injury, 156, 185, 310 Research Design, 31, 60, 311 Research Support, 50, 311 Resection, 56, 311 Respiration, 252, 258, 261, 293, 311 Respirator, 290, 311, 324 Respiratory failure, 5, 182, 311, 324 Respiratory Physiology, 311, 324 Restitution, 13, 51, 311 Restoration, 181, 294, 309, 310, 311, 325 Restrictive cardiomyopathy, 166, 311 Resuscitation, 27, 34, 98, 125, 311 Retinoblastoma, 208, 311 Retinoids, 53, 311

Retreatment, 311 Retrograde, 24, 67, 70, 143, 147, 155, 167, 168, 173, 311 Retroperitoneal, 4, 311 Retrospective, 51, 311 Retrospective Studies, 51, 311 Retroviral vector, 278, 311 Reversion, 259, 311 Rhamnose, 297, 311 Rheumatism, 312 Rheumatoid, 172, 224, 312 Rheumatoid arthritis, 172, 224, 312 Rhinitis, 222, 233, 312 Ribose, 248, 312 Risk factor, 15, 33, 47, 103, 178, 305, 312 Risk patient, 149, 176, 312 Rod, 262, 312 Rubber, 4, 247, 271, 312 S Saline, 35, 44, 56, 189, 312 Salivary, 298, 312 Saphenous, 189, 266, 312 Saphenous Vein, 189, 266, 312 Saponins, 312, 317 Sarcoid, 66, 166, 312 Sarcoidosis, 66, 312 Sarcoma, 172, 312 Sarcoplasmic Reticulum, 12, 36, 312 Scalpel, 11, 312 Schizoid, 312, 325 Schizophrenia, 233, 312, 313, 325 Schizotypal Personality Disorder, 268, 312, 325 Sciatic Nerve, 300, 313 Sclerosis, 209, 313 Sclerotherapy, 4, 313 Screening, 19, 49, 218, 263, 313 Secondary tumor, 291, 313 Secretion, 45, 262, 283, 285, 293, 300, 313 Sedentary, 8, 59, 313 Sediment, 313 Sedimentation, 5, 313 Seizures, 18, 268, 299, 313 Semen, 306, 313 Semisynthetic, 259, 260, 275, 313 Senescence, 47, 313 Sensibility, 250, 313 Sensor, 146, 147, 150, 174, 183, 313 Sepsis, 4, 22, 28, 313 Septal, 16, 79, 110, 313, 314 Septic, 224, 313 Septicemia, 28, 313

341

Septum, 16, 110, 138, 152, 188, 253, 259, 314 Septum Pellucidum, 314 Sequencing, 314, 319 Serotonin, 37, 296, 301, 309, 314, 322 Serum, 19, 22, 124, 264, 289, 308, 314 Serum Albumin, 308, 314 Sex Characteristics, 248, 314 Sex Determination, 209, 314 Shock, 63, 146, 149, 151, 159, 169, 171, 174, 176, 177, 178, 180, 224, 260, 283, 314, 321 Side effect, 39, 172, 181, 182, 183, 197, 199, 248, 255, 314, 321 Sigmoid, 4, 304, 314 Sigmoid Colon, 304, 314 Sigmoidoscope, 305, 314 Sigmoidoscopy, 4, 314 Signal Transduction, 14, 62, 314 Signs and Symptoms, 3, 18, 310, 314, 322 Sinoatrial Node, 138, 151, 167, 180, 186, 276, 315 Sinusal, 171, 315 Skeletal, 8, 43, 77, 262, 287, 294, 308, 312, 315, 322 Skeleton, 247, 287, 305, 315 Skull, 266, 315, 319 Sleep apnea, 15, 315 Small intestine, 262, 271, 278, 282, 286, 315 Smoking Cessation, 227, 315 Smooth muscle, 41, 257, 258, 293, 299, 315, 318 Soaps, 277, 315 Social Environment, 308, 315 Sodium, 20, 39, 45, 52, 67, 308, 315 Soft tissue, 61, 188, 189, 257, 315 Solitary Nucleus, 254, 315 Solvent, 274, 297, 315 Somatic, 248, 260, 291, 292, 300, 315, 323 Somatic cells, 260, 291, 292, 315 Sotalol, 76, 85, 109, 117, 131, 316 Sound wave, 265, 310, 316 Soybean Oil, 303, 316 Spatial disorientation, 270, 316 Specialist, 237, 269, 316 Species, 43, 255, 259, 274, 282, 288, 290, 291, 292, 293, 299, 302, 308, 309, 316, 317, 321, 324, 325 Specificity, 17, 28, 155, 248, 258, 316 Spectrin, 271, 316 Spectrum, 29, 54, 316 Sperm, 262, 316 Spinal cord, 221, 232

Spleen, 289, 312, 316 Sporadic, 311, 316 Stabilization, 111, 316 Standard therapy, 141, 157, 316 Statistically significant, 10, 316 Steady state, 20, 25, 63, 316 Steel, 165, 166, 262, 316 Stellate, 42, 316 Stellate Ganglion, 42, 316 Sterility, 285, 317 Steroid, 53, 259, 312, 317 Stimulant, 258, 270, 287, 317 Stimulus, 11, 28, 30, 37, 67, 140, 171, 180 Stomach, 247, 254, 269, 274, 278, 279, 282, 287, 294, 300, 301, 315, 316, 317 Stool, 4, 263, 287, 317, 319 Strand, 160, 317 Stress, 19, 33, 37, 38, 43, 45, 58, 84, 173, 254, 260, 292, 295, 298, 304, 312, 317, 323 Stroke, 27, 57, 148, 159, 165, 181, 204, 216, 259, 317 Stroke Volume, 148, 259, 317 Stump, 4, 317 Stupor, 294, 317 Styrene, 165, 312, 317 Subacute, 284, 317 Subarachnoid, 280, 317 Subclavian, 105, 254, 257, 317 Subclinical, 284, 313, 317 Subcutaneous, 251, 271, 299, 317 Subspecies, 316, 317 Substance P, 291, 313, 317 Substrate, 26, 39, 40, 41, 43, 56, 75, 76, 189, 272, 318 Suction, 189, 277, 318 Sudden cardiac death, 13, 17, 23, 27, 33, 40, 42, 44, 49, 54, 56, 63, 64, 150, 151, 159, 173, 180 Sudden death, 10, 12, 15, 17, 20, 22, 35, 37, 39, 49, 50, 54, 75, 101, 153, 318 Superior vena cava, 77, 89, 152, 257, 315, 318 Supine, 18, 45, 318 Supplementation, 10, 318 Support group, 50, 318 Suppression, 32, 54, 318 Survival Rate, 141, 157, 174, 318 Sympathectomy, 15, 318 Sympathetic Nervous System, 8, 18, 58, 66, 92, 254, 299, 318 Sympathomimetic, 270, 274, 287, 296, 318 Symphysis, 262, 306, 318

342

Tachycardia

Symptomatic, 4, 87, 127, 150, 194, 277, 298, 318 Synapse, 248, 295, 299, 304, 318, 321 Synapsis, 318 Synaptic, 55, 296, 314, 318 Synchrony, 143, 151, 158, 180, 319 Syncope, 9, 83, 103, 187, 215, 227, 319 Synergistic, 30, 55, 319 Systemic, 3, 7, 28, 45, 46, 63, 166, 252, 256, 268, 274, 281, 284, 308, 312, 313, 319, 323 Systemic disease, 4, 313, 319 Systole, 19, 143, 153, 168, 319 Systolic, 6, 22, 44, 59, 60, 144, 168, 228, 282, 319 Systolic blood pressure, 6, 319 Systolic heart failure, 44, 319 T Tachyarrhythmia, 27, 141, 146, 148, 149, 151, 153, 157, 159, 162, 171, 180, 183, 188 Tachycardia, Supraventricular, 12, 319 Tachycardia, Ventricular, 141, 182, 319 Tachypnea, 28, 254, 319 Telangiectasia, 209, 319 Telecommunications, 137, 319 Temporal, 16, 29, 54, 154, 250, 280, 290, 319 Tendon, 277, 319 Tenesmus, 4, 7, 319 Teratogenic, 269, 319 Thalamic, 156, 185, 253, 319 Thalamic Diseases, 253, 319 Theophylline, 9, 116, 123, 319 Therapeutics, 28, 198, 320 Thermal, 28, 35, 44, 122, 270, 296, 320 Thoracic, 15, 18, 30, 93, 95, 99, 103, 111, 189, 317, 320, 325 Thoracotomy, 17, 189, 320 Thorax, 247, 304, 318, 320, 323 Thrombin, 302, 306, 320 Thromboembolism, 232, 235, 320 Thrombomodulin, 306, 320 Thrombosis, 306, 313, 317, 320 Thromboxanes, 252, 320 Thrombus, 266, 284, 294, 302, 320 Thyroid, 32, 53, 219, 226, 229, 282, 320, 322 Thyroid Gland, 282, 320 Thyroid Hormones, 32, 320, 322 Tin, 302, 320 Tissue Culture, 10, 320 Tolerance, 15, 31, 46, 48, 247, 279, 320 Tomography, 4, 320 Tone, 8, 127, 178, 321

Tonicity, 281, 321 Tonus, 321 Tooth Preparation, 248, 321 Topical, 274, 315, 321 Torsades de Pointes, 38, 85, 117, 153, 321 Torsion, 284, 321 Toxic, iv, 5, 43, 253, 259, 267, 269, 273, 296, 302, 317, 321 Toxicity, 74, 100, 172, 270, 321 Toxicokinetics, 321 Toxicology, 206, 321 Toxin, 273, 320, 321 Trachea, 257, 287, 301, 320, 321 Traction, 262, 321 Transduction, 15, 45, 62, 314, 321 Transfection, 256, 272, 278, 321 Transillumination, 61, 321 Translational, 40, 321 Transmitter, 247, 270, 286, 290, 296, 321 Transplantation, 43, 62, 262, 283, 290, 321 Trauma, 28, 80, 94, 268, 298, 321 Trees, 312, 322 Tremor, 209, 322 Trichomoniasis, 292, 322 Tropomyosin, 322 Troponin, 83, 84, 322 Tryptophan, 263, 314, 322 Tuberous Sclerosis, 102, 209, 322 Tumour, 277, 322 Type 2 diabetes, 6, 230, 322 Tyrosine, 58, 270, 322 U Ulcerative colitis, 7, 230, 285, 322 Ultrasonography, 18, 45, 322 Unconscious, 169, 178, 250, 254, 283, 322 Unsaturated Fats, 277, 322 Uraemia, 298, 322 Urethane, 165, 322 Urethra, 300, 306, 322, 323 Urinary, 4, 45, 323 Urinary Retention, 4, 323 Urinate, 323 Urine, 5, 256, 266, 270, 281, 282, 287, 298, 306, 322, 323 Urticaria, 234, 323 Uterine Contraction, 259, 323 Uterus, 261, 266, 267, 273, 291, 305, 323 V Vaccine, 306, 323 Vagal, 8, 9, 17, 18, 30, 137, 178, 323 Vagotonia, 86, 323 Vagus Nerve, 29, 137, 315, 323

343

Valves, 49, 138, 140, 144, 152, 323 Varicose, 287, 313, 323 Varicose Ulcer, 287, 323 Varicose vein, 313, 323 Vascular endothelial growth factor, 156, 185, 323 Vascular Resistance, 43, 45, 250, 255, 323 Vasculitis, 298, 323 Vasoactive, 15, 63, 323 Vasoconstriction, 8, 17, 43, 156, 185, 270, 274, 323 Vasodilatation, 260, 296, 323 Vasodilation, 8, 184, 296, 299, 323 Vasodilator, 8, 15, 257, 270, 294, 299, 323 Vasomotor, 323, 324 Vector, 168, 187, 321, 324 Vein, 91, 189, 250, 254, 286, 296, 299, 312, 317, 318, 324 Vena, 152, 324 Venous, 18, 45, 46, 138, 161, 166, 235 Venous blood, 138, 256, 324 Venous Pressure, 18, 48, 261, 324 Ventilation, 9, 19, 117, 125, 324 Ventilator, 290, 311, 324 Ventricular Dysfunction, 15, 48, 58, 60, 178, 271, 324 Ventricular fibrillation, 10, 13, 16, 20, 34, 35, 39, 42, 59, 63, 66, 141, 145, 146, 148, 149, 150, 151, 153, 155, 157, 158, 159, 162, 165, 169, 171, 173, 176, 178, 180, 183, 186

Ventricular Function, 47, 58, 81, 87, 309, 324 Venules, 256, 258, 324 Verapamil, 77, 93, 112, 117, 121, 123, 128, 324 Vertebrae, 316, 324 Vertebral, 29, 324 Vesicular, 268, 281, 324 Veterinary Medicine, 205, 324 Viral, 38, 278, 290, 297, 321, 324 Virulence, 253, 321, 324 Virus, 225, 254, 261, 278, 302, 311, 321, 324 Visceral, 254, 300, 323, 325 Visceral Afferents, 254, 323, 325 Vitro, 12, 16, 25, 28, 37, 40, 43, 59, 325 Vivo, 12, 16, 25, 26, 28, 36, 40, 53, 58, 59, 325 W Wakefulness, 267, 325 White blood cell, 28, 251, 288, 289, 293, 302, 325 Windpipe, 257, 301, 320, 325 Withdrawal, 18, 268, 295, 325 Womb, 26, 323, 325 Wound Healing, 156, 185, 325 X Xenograft, 251, 325 X-ray, 41, 53, 265, 277, 296, 308, 309, 325 Y Yawning, 295, 325 Yeasts, 301, 325 Z Zymogen, 306, 325

344

Tachycardia